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Abstract

Cervical cancer is a serious health problem around the world, especially in poor and developing areas where the disease is often diagnosed late, leading to high death rates. Although current treatments have helped improve survival, they can cause strong side effects and sometimes stop working due to drug resistance. Natural plant compounds such as curcumin, withaferin A, piperlongumine, piperine, resveratrol, and baicalein have shown good anticancer effects. They help by causing cancer cells to die, stopping cancer spread, and controlling important pathways like NF-?B, Akt, JAK/STAT, and HPV E6/E7. However, these compounds do not dissolve well and are poorly absorbed in the body, which limits their medical use. Therefore, modern drug delivery systems like nanoparticles and solid lipid nanoparticles (SLNs) are needed to improve their effectiveness. Overall, herbal medicines show good potential as supportive treatments for cervical cancer, but more clinical studies are still required.

Keywords

Cervical cancer, Herbal therapeutics, Phytochemicals, HPV oncogenes, Apoptosis, Solid lipids nanoparticles (SLNs)

Introduction

Cervical cancer continues to be a major and widely occurring malignancy among women worldwide., with its impact being particularly severe In developing and middle-income nations [1] . The epidemiological burden is especially significant in India [2] , where an estimated 122,844 women are newly diagnosed each year and approximately 67,477 die from the disease [3] . India has the highest rate of cervical cancer in South Asia, with about 22 cases per 100,000 women. This is higher than Bangladesh (19.2), Sri Lanka (13), and Iran (2.8) [4] .  In countries such as Mexico, cervical cancer leads to the death of more than 4,000 women annually, underscoring the urgent need to improve therapeutic strategies, particularly for cases identified at locally advanced stages  [5] . Cervical cancer typically originates in the lower portion of the uterus, at the junction where it meets the vagina. The disease progresses through several distinct stages, as illustrated in (Fig. 1) [6] . The heaviest burden is observed in Sub-Saharan Africa, where insufficient screening, low awareness, and lack of proper healthcare contributes to high disease and death rates [7].

Fig.1: Stages of cervical cancer [6]

In 2020, India accounted for approximately 21% of newly diagnosed global cervical cancer cases and 23% of related deaths [8]  . Over 120,000 women develop the disease each year in the country, and more than 75,000 lose their lives due to delayed screening and inadequate early detection [9] . Persistent infection with high-risk HPV, particularly HPV-16 and HPV-18, is the leading cause of cervical cancer[10] .  Because early-stage disease often presents with minimal or no symptoms, regular screening techniques such as Pap smears and HPV DNA testing are essential for timely diagnosis [11] . At the molecular level, cervical cancer involves dysregulation of pathways controlling inflammation, cell proliferation, and survival [12] . Anti-apoptotic proteins such as Bcl-2 become overexpressed, whereas pro-apoptotic proteins including Bax and caspases (3, 8, 9) are suppressed. This imbalance enables cancer cells to resist programmed cell death [13] . Additionally, angiogenic mediators such as VEGF support tumor growth and promote vascularization [14] . 

Pathophysiology of cervical cancer are :- 

Step 1: HPV Infection :  HPV enters cervical epithelial cells through minor abrasions or sexual contact and attaches to surface receptors such as heparan sulfate [15,16] .

Step 2: Viral Replication :  The viral DNA moves into the cell nucleus, and proteins E1 and E2 help manage its replication[17,18] .

Step 3: Integration and Oncogenesis : The viral DNA joins the host DNA, causing high levels of E6 and E7 proteins that turn off tumor-fighting proteins p53 and Rb, leading to uncontrolled cell growth and cancer[19–21] .

Step 4: Immune Evasion : HPV-infected cells evade immune detection by suppressing immune responses and downregulating MHC class I and II molecules [20,22,23] .

Step 5: Angiogenesis and Metastasis: Tumor cells stimulate new blood vessel formation and invade surrounding tissues, eventually spreading to distant organs [24,25] .

Table 1:- Complications and Associated Diseases in Women with Cervical Cancer

Complication/disease

cause

Symptoms

Urinary Tract Infections (UTI) (20%)

Radiation or tumor pressure in the bladder

Burning during urination, frequent urination

Pelvic Inflammatory Disease (PID) (15%)

Weak immune defense or infection spread

Pelvic pain, fever, discharge

Vaginal Infections (15%)

Damage to the vaginal lining during treatment

Itching, discharge, foul odor

Anemia (20%)

Excessive bleeding or chemo side effects

Fatigue, pale skin, weakness

Mental Health Issues (15%)

stress, body changes

Depression, anxiety, sleep problems

Gastrointestinal problems (15%)

Radiation effects on the intestine

Diarrhea, cramps, constipation

Cervical cancer affects multiple organ systems beyond the cervix itself [26] . As the disease advances and treatments such as chemotherapy, radiotherapy, or surgery are administered, patients often experience additional health issues known as complications or comorbidities. These complications may arise either directly from tumor growth or as adverse effects of treatment modalities, frequently requiring further medical care [27,28] .

Table 2. Probable Causes of Cervical Cancer

Cause

Explanation

HPV infection

Most common reason. It spreads during sex. HPV types 16 & 18 cause 70% of cases [10]

Lack of HPV vaccination:

Girls who don’t get the HPV vaccine early are at higher risk of getting infected later in life [31]

Smoking

Increases the risk of cervical cancer by damaging cervical cells and lowering immune defence [11]

Genetic predisposition

If close relatives had cervical cancer, the chances are slightly higher for you too [11]

Poor genital hygiene

Not keeping private parts clean can lead to infections and increase the risk of cervical cancer [11]

Prevention and New Technologies :

Recent technological advancements have significantly improved cervical cancer prevention and early detection [29] . Visual Inspection with Acetic Acid (VIA) is becoming increasingly accessible and serves as a simple, low-cost, and reliable screening method suitable for primary healthcare settings [30,32] . ne major advantage of VIA is its ability to provide immediate results, facilitating a “see-and-treat” approach in which precancerous lesions are treated on the same day using cryotherapy, thereby improving patient compliance [32] . One major advantage is that VIA provides instant results, allowing same-day treatment of precancerous lesions with cryotherapy at the same facility. This “see-and-treat” approach enhances treatment adherence and reduces patient loss to follow-up [33] . Additionally, newer HPV vaccines administered to girls aged 9–14 offer strong protection against cervical cancer and represent a major public health advancement [34] .

CONVENTIONAL THERAPY OF CERVICAL CANCER :

Conventional therapy for cervical cancer refers to established, evidence-based treatment modalities that have been widely used and validated over time [35] . These therapies encompass surgery, radiation therapy, chemotherapy, and their combinations, tailored to the cancer's stage and individual patient factors [36] .

Definitive Chemoradiation (CRT) in Cervical Cancer :

For cervical cancer patients in FIGO stages IIB to IVA, chemoradiation is the main treatment. Studies show that adding cisplatin-based chemotherapy helps patients live longer, although it can cause short-term side effects like stomach problems and bone marrow suppression. However, it does not increase long-term side effects. At present, the standard treatment uses chemoradiation with weekly or every-three-week cisplatin, along with external beam radiation therapy and a brachytherapy boost.

Definitive Intensity-Modulated Radiation Therapy (IMRT) :

IMRT has been shown to improve outcomes for cervical cancer patients [39]. In a randomised study by Gandhi et al. (2021), 44 patients were assigned to receive either conventional three-dimensional radiation or IMRT, IMRT significantly reduced grade ≥2 acute GI toxicities and long-term GI problems [40]  Some patients in this trial also had PET/CT scans to precisely outline functional bone marrow, helping to further reduce bone marrow suppression [41] . IMRT in these cases lowered severe neutropenia and GI toxicity compared to historical rates for example, when giving 45 Gy in 25 fractions to the whole pelvis and prophylactic lymph nodes, an additional boost of 55.0–57.5 Gy to involved nodes achieved high complete response rates on PET/CT after 3 months [42] . This SIB technique is now widely adopted, and the EMBRACE II study is actively evaluating IMRT and image-guided radiation therapy (IGRT) approaches with SIB for cervical cancer [43].

Image-Guided Radiation Therapy (IGRT) :

IGRT is important because it allows IMRT to deliver radiation very accurately, which helps protect nearby healthy tissues from damage. CBCT is the most commonly used technique in IGRT. Using CBCT images every day helps doctors correct patient positioning mistakes and reduces the need for large treatment margins [45] .

Proton Beam Therapy (PBT) :

A Japanese study of 25 cervical cancer patients treated with proton boost achieved excellent local control at five years — 100% for stage IIB and 61% for stage IIIB/IVA — and long-term survival rates of 89% and 40%, respectively [46] .  Modern IMPT (intensity-modulated proton therapy) can deliver better cumulative doses to tumors while sparing healthy tissues compared to VMAT [47] . Dosimetric comparison studies between IMPT and IMRT have shown 20–40% improvement in bone marrow sparing [48] . Ovarian-sparing Therefore, brachytherapy remains the standard of care for locally advanced cervical cancer. Dosimetric studies have shown that PBT can significantly reduce radiation dose to both the small and large bowel while still delivering an optimal dose to the target tumor area [49,50] . This advantage is especially important when treating para-aortic lymph nodes, as PBT also lowers the dose to critical organs such as the kidneys and spinal cord [51] . Since whole pelvic radiation therapy can cause premature menopause in younger patients, a study evaluated ovarian-sparing IMPT versus volumetric modulated arc therapy (VMAT) [52,53] . The study found that all IMPT plans succeeded in sparing the ovaries, whereas on ly 40% of VMAT plans were able to achieve ovarian sparing [54] .

Several treatment plans have successfully achieved a mean ovarian dose (Dmean) below 15 Gy while maintaining adequate target coverage [55] . There is growing clinical evidence supporting the use of proton therapy for gynecological cancers [56] . One study reported outcomes for 11 women treated with pencil beam scanning intensity-modulated proton therapy (IMPT) after hysterectomy for gynecologic malignancies. The toxicity profile was favorable, with only one case of grade 3 acute gastrointestinal toxicity and no grade 3 or higher genitourinary toxicities [57] . Ongoing prospective studies (e.g., NCT03184350) are investigating the role of proton beam therapy (PBT) for post-operative uterine and cervical cancers [58,59] .  However, further research is needed to confirm the long-term oncological outcomes of PBT compared to IMRT-based treatments in larger patient populations.

 Current Drugs For Cervical Cancer Treatment :

In early-stage cervical cancer, surgery can often cure the disease. Chemotherapy is mainly used for most other patients. For very small tumors (stage IA1) or small localized tumors (IB1 and IIA1), treatments like conization or hysterectomy can successfully cure the cancer. In more advanced stages, the usual treatment is radiation therapy combined with cisplatin-based chemotherapy. Other chemotherapy drugs, such as paclitaxel, vincristine, gemcitabine, and 5-fluorouracil, can improve the effect of radiation or work together with cisplatin to kill more cancer cells. However, using chemotherapy alone is not very effective in advanced cervical cancer[64] .

HERBAL MEDICINES USED IN THE TREATMENT OF CERVICAL CANCER:-

Curcumin in the Treatment of Cervical Cancer:- Curcumin, a naturally occurring polyphenolic compound derived from the rhizome of Curcuma longa (turmeric), has gained significant attention due to its broad-spectrum pharmacological activities and potent anticancer properties [65] . It is an orange-yellow crystalline compound with a slightly bitter taste, having the molecular formula C??H??O? and a molecular weight of 368.37 g/mol [66]  (Fig. 2) . Curcumin has beneficial effects in many health problems, including inflammation, oxidative stress, metabolic diseases, and cancer. It shows anti-inflammatory, antioxidant, blood pressure–lowering, fat-reducing, antibacterial, liver-protective, and anticancer activities. Curcumin helps kill cancer cells by activating caspase-3 and caspase-9, which cause programmed cell death. It also blocks important proteins like NF-κB and AP-1 that play a major role in inflammation and cancer growth [69]  (Fig 3) .  Moreover, curcumin causes cell cycle arrest at the G2/M phase and enhances the production of reactive oxygen species (ROS), thereby promoting oxidative stress-mediated apoptosis in cervical cancer cells [70] .  Animal model experiments further demonstrated tumor regression and enhanced apoptosis upon curcumin administration [71]. Additionally, when used in combination with standard chemotherapeutic agents such as cisplatin, curcumin enhances cytotoxic activity while reducing the side effects associated with chemotherapy [72] . These findings highlight its potential as a promising adjuvant in cervical cancer therapy [73] . However, despite its remarkable pharmacological benefits, the clinical application of curcumin is limited due to its poor aqueous solubility, low bioavailability, and rapid systemic metabolism [74] . To overcome these limitations, researchers are developing novel formulations such as curcumin-loaded nanoparticles, liposomes, and solid lipid nanoparticles (SLNs) to improve its stability, absorption, and therapeutic efficacy [75] . Thus, curcumin represents a valuable natural compound with promising potential in the prevention and treatment of cervical cancer, particularly when delivered through advanced nanocarrier systems [76] .

Drug :- Curcumin

Molecular structure:

Fig.2 : Chemical Structute of Curcumin

Source :- Curcumin, a principal curcuminoid, is naturally sourced from the rhizome of Curcuma longa (Turmeric) L. (Zingiberaceae family) .

Molecular formula:- C??H??O?

IUPAC Name :- (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione

Mechanism of Curcumin against Cervical Cancer :- Curcumin induces apoptosis, arrests cell cycle, inhibits NF-κB, downregulates HPV E6/E7, increases ROS, and synergizes with chemotherapeutic drugs [77,78] .

Fig . 3 :  Mechanism of curcumin

Withaferin A in the Treatment of Cervical Cancer :- Withaferin A (WFA)  is a bioactive steroidal lactone obtained from Withania somnifera, a medicinal herb widely known as ashwagandha [79,80] (Fig.4) . Traditionally, ashwagandha has been used for centuries to manage several ailments such as epilepsy, depression, arthritis, and diabetes [81] .  In recent years, scientific attention has shifted toward its principal active compound, WFA, due to its potent cytotoxic and anticancer potential against various types of cancers [82] . The anticancer action of WFA is attributed to multiple cellular and molecular mechanisms. Suppression of Akt and NF-κB signaling pathways to induce apoptosis [83] . Downregulation of the anti-apoptotic protein Bcl-2 Cell cycle arrest at the G2/M phase [84] . Stimulation of reactive oxygen species (ROS) generation . Promotion of Par-4 expression [85].  Activation of caspases 3 and 9, DNA damage, and inhibition of HSP90 activity [86,87] .

 Drug :-  Withaferin A

Molecular structure :-

Fig.4: Chemical Structure of  Withaferin A

Source :- Roots and leaves of Withania somnifera (Ashwagandha)

Molecular formula:- C28H38O6

IUPAC Name:- (4β,5β,6β,22R)-5,6-epoxy-4,22,27-trihydroxy-1-oxowitha-2,24-dienolide

Mechanism of Withaferin A against Cervical Cancer :- Suppresses Akt and NF-κB signaling, downregulates Bcl-2, arrests G2/M phase, increases ROS, promotes Par-4 expression, activates caspases 3 and 9, induces DNA damage, inhibits HSP90, and induces apoptosis [88,89,90] (Fig.5).

Fig.5: Mechanism of withaferin A

Piperlongumine in the Treatment of Cervical Cancer :- Piperlongumine (PL) is a natural alkaloid found in Piper longum (long pepper), known for its strong antioxidant and anticancer properties [91]  (Fig.6) . Piperlongumin also decreases Bcl-2 (anti-apoptotic) and increases Bax (pro-apoptotic) protein levels, promoting cell death in cervical cancer cells such as HeLa and SiHa [92]. Studies from 2023–2025 have shown that Piperlongumine effectively reduces cancer cell growth and works well with chemotherapy drugs, making treatment more effective and less toxic [93,94]. However, its poor solubility and low stability limit clinical use .

Drug :- Piperlongumine (Piper longum (long pepper)

Molecular structure :- Piperlongumine

Fig.6: Chemical Structure of Piperlongumine

Source :- Naturally obtained from the fruits and roots of Piper longum (Indian long pepper), belonging to the Piperaceae family

Molecular formula:- C17H19NO5

IUPAC Name:- (E,E)-1-(3,4,5-trimethoxyphenyl)-5-(3-pyridinyl)-1,4-pentadien-3-one

Piperine in the Treatment of Cervical Cancer :- Piperine is a natural alkaloid found in Piper nigrum (black pepper) and Piper longum (long pepper), known for its strong antioxidant and anticancer effects [95] (Fig.7) . It causes cell cycle arrest at the G1/G0 and G2/M phases, stopping cancer cell division [96] . Studies have shown that piperine can enhance the effect of chemotherapy while lowering its toxicity [97,98] . However, due to its poor solubility and bioavailability, advanced formulations such as piperine-loaded nanoparticles, liposomes, and SLNs are being developed [99,100] . Thus, piperine is a promising herbal compound for cervical cancer therapy [101] .

Drug :- Piperine (Piper nigrum and Piper longum)

Source :- Piperine is primarily isolated from the fruits of black pepper (Piper nigrum) and long pepper (Piper longum), family Piperaceae

Molecular formula :- C17H19NO3

Molecular structure :-

Fig.7: Chemical Structure of Piperine

IUPAC Name :- (2E,4E)-5-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylpenta-2,4-dien-1-one

Resveratrol as a Herbal Medicine for the Treatment of Cervical Cancer :- Resveratrol is a naturally occurring polyphenolic compound that belongs to the class of phytoalexins [102] (Fig.8). It is mainly found in grapes, blueberries, peanuts, and red wine. Because it is plant-derived, resveratrol is considered a herbal compound, Various studies have demonstrated that resveratrol possesses strong anticancer potential against cervical cancer [103] . In cell-based (in vitro) and animal (in vivo) studies, resveratrol has been shown to suppress cancer cell growth, induce apoptosis, and arrest the cell cycle [104] . Although these findings highlight resveratrol as a promising herbal anticancer agent, its clinical use is still limited due to poor bioavailability [105,106]. Therefore, developing novel formulations such as nanoparticles, liposomes, or solid lipid nanoparticles (SLNs) could enhance its absorption and therapeutic effectiveness [107] .  Overall, resveratrol can be regarded as a potent plant-based compound with significant potential for the herbal treatment and prevention of cervical cancer [108] .

Drug :- Resveratrol (red grapes)

Molecular structure:- Resveratrol

Fig.8: Chemical Structure of Resveratrol

Source :- Resveratrol is a natural polyphenol found in grapes, red wine, peanuts, and berries (especially in the skin of red grapes).

Molecular Formula: - C14H12O3

IUPAC Name : 5-[(E)-2-(4-hydroxyphenyl)ethenyl]benzene-1,3-diol

Scutellaria baicalensis (Huang Qin) in the Treatment of Cervical Cancer :-  Scutellaria baicalensis, commonly known as Huang Qin, is a traditional Chinese medicinal herb whose major bioactive compound, baicalein (Fig.9) , is extracted from its roots [109,110] . Baicalein possesses several pharmacological activities, including antioxidant, anti-inflammatory, anti-allergic, and antitumor effects [111]. Research has demonstrated that baicalein can inhibit the progression of various cancers such as breast, bladder, and ovarian cancer [112] . In cervical cancer, baicalein has been found to significantly suppress the proliferation of HeLa and SiHa cells in a time- and dose-dependent manner, indicating its strong antitumor potential [113] .

Drug:- Baicalin

Molecular structure :-

Fig.9: Chemical Structure of Baicalin

Source :- Scutellaria baicalensis — commonly known as Chinese skullcap, a medicinal herb widely used in traditional Chinese medicine.

Molecular Formula :- C15H10O5

IUPAC Name :- (2S,3S,4S,5R,6S)-6-(5,6-dihydroxy-4-oxo-2-phenylchromen-7-yl)oxy-3,4,5-trihydroxyoxane-2-carboxylic acid

Ganoderma lucidum (Ling Zhi) in the Treatment of Cervical Cancer :- Ganoderma lucidum, commonly known as Ling Zhi, is a highly valued medicinal mushroom that has been used in traditional Chinese medicine for more than 2000 years [114] . Extracts from this fungus, particularly Ganoderma lucidum polysaccharides (GLP) and Ganoderma acids, have been utilized to treat various diseases due to their anti-inflammatory, antioxidant, immunomodulatory, and anticancer properties [115] . Molecular structure of Ganoderic acid A  (Fig.10) . Recent research has revealed that GLP suppresses the JAK/STAT5 signaling pathway, which is essential for cell proliferation and survival [116] .  Additionally, GLP has been found to inhibit the epithelial–mesenchymal transition (EMT) , a key process responsible for cancer cell invasion and metastasis [117] .  The transwell migration assay confirmed that GLP significantly reduced the invasion and migration potential of cervical cancer cells [118]  . Overall, these findings indicate that Ganoderma lucidum polysaccharides exhibit strong anticancer activity in cervical cancer by inhibiting cell growth, triggering apoptosis, and reducing metastatic behavior [119] .

Drug:- Ganoderic acid A

Molecular structure :- Ganoderic acid A

Fig.10: Chemical Structure of Ganoderic acid A

Source :- Ganoderma lucidum — a medicinal mushroom that grows on decaying hardwood trees like oak and maple.

Molecular Formula :- C??H??O?

IUPAC Name :- 25R)-7β,15α-Dihydroxy-3,11,23-trioxolanost-8-en-26-oic acid.

Camptotheca acuminata (X? Shù) in the Treatment of Cervical Cancer :- Camptotheca acuminata, commonly known as Xi Shu, is a medicinal tree whose bark and fruits contain potent anticancer alkaloids, primarily camptothecin (CPT) [120,121] (Fig.11) . To overcome its poor solubility and limited bioavailability, several camptothecin derivatives, such as irinotecan and topotecan, have been developed and are now widely used in chemotherapy for various cancers, including cervical cancer [122] . Clinical studies by the European Organization for Research and Treatment of Cancer (EORTC) evaluated irinotecan (350 mg/m² every three weeks) as a first-line chemotherapeutic agent for cervical cancer [123] .  The study reported an overall response rate of 15%, with 24% of patients responding in non-irradiated regions (Group A), while no responses were observed in previously irradiated regions (Group B) [124]. However, adverse effects such as myelosuppression, diarrhea, and dehydration were noted, leading to a few treatment-related deaths. These findings indicate that, although camptothecin derivatives show significant therapeutic potential against cervical cancer, further research is required to reduce gastrointestinal toxicity and improve treatment safety [125,130] .

Drug :- Camptothecin

Molecular structure :- Camptothecin

Fig.11: Chemical Structure of Camptothecin

Source :- Obtained from the bark and fruits of Camptotheca acuminata (Chinese tree of life or Xi Shu).

Molecular Formula: - C20H16N2O4

IUPAC Name :- (S)-4-ethyl-4-hydroxy-1H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-dione.

Terminalia catappa (Lan Ren Shu) in the Treatment of Cervical Cancer :- Terminalia catappa contains a wide variety of phytoconstituents present in its leaves, fruits, and seeds. Several studies have reported that extracts of T. catappa exhibit antibacterial, anti-inflammatory, hepatoprotective, and anticancer properties and also the bioactive compund are Ellagic acid (Fig.12) . In one study, the ethanolic extract of T. catappa (TCE) showed a significant antimetastatic effect on cervical cancer cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) [131,132] . Furthermore, research published in the Journal of Toxicology investigated the cytotoxic activity of endophytic fungal extracts (N97) isolated from T. catappa against human cervical cancer cells [133,134,135] . At the maximum tested concentration (100 µg/mL), ERK1/2 phosphorylation was reduced by approximately 46%, as evidenced by Western blot analysis [136,137] .

Drug :-  Ellagic Acid                           

Molecular structure :-

Fig.12: Chemical Structute of Ellagic Acid

Source :- Terminalia catappa is primarily sourced from the tropical Indian almond tree.

Molecular Formula: - C??H?O?

IUPAC  Name :- 6,7,13,14-tetrahydroxy-2,9-dioxatetracyclo[6.6.2.04,16.011,15]hexadeca-1(15),4,6,8(16),11,13-hexaene-3,10-dione

Antrodia cinnamomea (Niu-Chang-Chih) in the Treatment of Cervical Cancer :- In Traditional Chinese Medicine, Antrodia cinnamomea (Antrodia camphorata) is commonly consumed as a medicinal food [138] . Its crude extracts exhibit a wide range of biological properties, and much scientific attention has focused on its anticancer potential [139] , and their bioactive compond of antrodia cinnamomea (Fig.13) . Several studies have also reported its hepatoprotective and liver-protecting activities. When the lyophilized mycelial powder of A [140] camphorata was dissolved in distilled water, it was found to be safe and non-toxic. In the context of cervical cancer, extracts of A. camphorata were shown to trigger apoptosis in HeLa and C-33A cell lines [141]. This apoptotic response involved activation of caspase-3, caspase-8, and caspase-9, along with increased cytochrome c release [142] . The extract also upregulated pro-apoptotic  and upregulation of pro-apoptotic proteins such as Bad, Bak, and Bim [143] . The extract showed antiproliferative effects by inducing G2/M phase cell cycle arrest in cervical cancer cells [144] . Yng et al. demonstrated that treating HeLa and C-33A cells with A. camphorata extract (10–1000 µg/mL) reduced cell viability in a dose- and time-dependent manner as shown by the MTT assay [145,146] . Higher concentrations further increased activation of caspase-3, caspase-8, and caspase-9 and elevated cytosolic cytochrome levels [147] . Expression of Bak, Bad, and Bim increased, while levels of Bcl-2 and Bcl-xL were reduced at higher doses [150] . Overall findings indicate that A. camphorata activates both intrinsic and extrinsic apoptotic pathways and exhibits strong cytotoxic effects on cervical cancer cells [148] . Therefore, A. camphorata may be considered a promising phytotherapeutic or adjunct treatment candidate for cervical cancer [149] .

Drug :- Ergosterol

Molecular structure :- bioactive compound of Ergosterol

Fig.13: Chemical Structure of Ergosterol

Source :- Antrodia cinnamomea is a rare medicinal mushroom found only in Taiwan, naturally growing inside the heartwood of the Niu-Chang (Cinnamomum kanehirae) tree.

Molecular Formula :- C28H44O

IUPAC  Name :- (3β)-ergosta-5,7,22-trien-3-ol

Chelidonium majus (Bai-Qu-Cai) :- Chelidonium majus (greater celandine) contains several isoquinoline alkaloids such as sanguinarine, chelidonine (Fig.14), chelerythrine, berberine, and coptisine in its roots, shoots, and leaves [150] . These compounds, especially chelidonine, show cytotoxic effects against leukemia, pancreatic (PANC-1), and colon (HT-29) cancer cells [151] . Research also identified a new nucleic acid–binding protein, CmMLP1, in the plant’s latex, which is highly expressed during plant development. CmMLP1 exhibits strong cytotoxicity toward cervical cancer cells, reducing the viability of HPV-positive HeLa cells more significantly than HPV-negative C33A cells [152,153] .

Drug :- Chelidonine

Molecular structure :-  Bioactive alkaloid of Chelidonine

Fig.14: Chemical Structure of Chelidonine

Source :- Chelidonium majus is sourced from a medicinal herb native to Europe and Western Asia.

Molecular Formula :- C20H19NO5

IUPAC  Name :- (5β)-5,6,7,8,15,16-Hexahydro-5-methyl-8,14-dioxabenzo[6,7]cyclohepta

[1,2-b]isoquinolin-13(5H)-one.

Myrica cerifera (Y´ angm´ei) :- Myrica cerifera (Yangmei) extract has been reported to provide anticancer benefits along with hepatoprotective and apoptosis-inducing effects. Studies on the diarylheptanoid compound myricanone, isolated from its ethanolic extract, showed significant cytotoxicity against HeLa cells and induced G0/G1 cell cycle arrest [154] .

Lycopodium clavatum (Jin Bu Huan) :- Alcohol-based extracts of Lycopodium clavatum have been used to support the treatment of liver diseases and Alzheimer’s disease. Research has shown that this extract can protect mice from liver cancer–causing chemicals. In HeLa cervical cancer cells, lycopodine showed strong anticancer activity by causing changes in DNA structure, increasing cell death, breaking DNA into fragments, and activating caspase-3 [156,157] .

CONCLUSION

Herbal compounds show strong potential against cervical cancer by stopping cancer cell growth, inducing apoptosis, reducing metastasis, and supporting conventional treatments. Although their low solubility and bioavailability are challenges, advanced delivery systems like nanoparticles can improve their effectiveness. Overall, herbal therapeutics offer a safe and promising approach for future cervical cancer management.

REFERENCES

  1. Hull, R., Mbele, M., Makhafola, T., Hicks, C., Wang, S. M., Reis, R. M., ... & Dlamini, Z. (2020). Cervical cancer in low and middle income countries. Oncology letters, 20(3), 2058-2074.
  2. Sreedevi, A., Javed, R., & Dinesh, A. (2015). Epidemiology of cervical cancer with special focus on India. International journal of women's health, 405-414.
  3. Sharma, N., Upadhyay, S., Gupta, P. C., & Katiyar, P. (2024). Cervical Cancer: Basic Information and Comprehensive Control. In Women's Health: A Comprehensive Guide to Common Health Issues in Women (pp. 129-158). Bentham Science Publishers.
  4. Arango-Bravo, E. A., del Carmen Cetina-Perez, L., Galicia-Carmona, T., Castro-Eguiluz, D., Gallardo-Rincon, D., Cruz-Bautista, I., & Duenas-Gonzalez, A. (2022). The health system and  access to treatment in patients with cervical cancer in Mexico. Frontiers in Oncology, 12, 1028291.
  5. Prat, J. (2015). Pathology of cancers of the female genital tract. International Journal of Gynecology & Obstetrics, 131, S132-S145.
  6. Omotoso, O., Teibo, J. O., Atiba, F. A., Oladimeji, T., Paimo, O. K., Ataya, F. S., ... & Alexiou, A. (2023). Addressing cancer care inequities in sub-Saharan Africa: current challenges and proposed solutions. International Journal for Equity in Health, 22(1), 189.
  7. Togashi, K., Morikawa, K., Kataoka, M. L., & Konishi, J. (1998). Cervical cancer. Journal of Magnetic Resonance Imaging, 8(2), 391-397.
  8. Singh, D., Vignat, J., Lorenzoni, V., Eslahi, M., Ginsburg, O., Lauby-Secretan, B., ... & Vaccarella, S. (2023). Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. The lancet global health, 11(2), e197-e206.
  9. Ramakrishnan, S., Partricia, S., & Mathan, G. (2015). Overview of high-risk HPV's 16 and 18 infected cervical cancer: pathogenesis to prevention. Biomedicine & pharmacotherapy, 70, 103-110.
  10. Tsikouras, P., Zervoudis, S., Manav, B., Tomara, E., Iatrakis, G., Romanidis, C., ... & Galazios, G. (2016). Cervical cancer: screening, diagnosis and staging. J buon, 21(2), 320-325.
  11. Li, X., Jiang, S., & Tapping, R. I. (2010). Toll-like receptor signaling in cell proliferation and survival. Cytokine, 49(1), 1-9.
  12. Hartman, M. L., & Czyz, M. (2020). BCL-w: apoptotic and non-apoptotic role in health and disease. Cell Death & Disease, 11(4), 260.
  13. Vimalraj, S. (2022). A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions. International Journal of Biological Macromolecules, 221, 1428-1438.
  14. Martinezi, A. G., Kumar, P. S., Hernandez-Kapila, Y. L., & Ambalavanan, N. (2024). Pathology and management of periodontal problems associated with viral infection, including HIV, COVID, and Others. Newman and Carranza's Clinical Periodontology: 4th South Asia Edition-E-Book, 267.
  15. Johnson, K. M., Kines, R. C., Roberts, J. N., Lowy, D. R., Schiller, J. T., & Day, P. M. (2009). Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. Journal of virology, 83(5), 2067-2074.
  16. Swindle, C. S., Zou, N., Van Tine, B. A., Shaw, G. M., Engler, J. A., & Chow, L. T. (1999). Human papillomavirus DNA replication compartments in a transient DNA replication system. Journal of virology, 73(2), 1001-1009.
  17. Chiang, C. M., Ustav, M., Stenlund, A., Ho, T. F., Broker, T. R., & Chow, L. T. (1992). Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proceedings of the National Academy of Sciences, 89(13), 5799-5803.
  18. Li, J., & Li, S. (2025). From Viral Infection to Genome Reshaping: The Triggering Role of HPV Integration in Cervical Cancer. International Journal of Molecular Sciences, 26(18), 9214.
  19. Vousden, K. (1993). Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes. The FASEB journal, 7(10), 872-879.
  20. Steinbach, A., & Riemer, A. B. (2018). Immune evasion mechanisms of human papillomavirus: An update. International journal of cancer, 142(2), 224-229.
  21. Bubeník, J. (2003). Tumour MHC class I downregulation and immunotherapy. Oncology reports, 10(6), 2005-2008.
  22. Zetter, B. R. (1998). Angiogenesis and tumor metastasis. Annual review of medicine, 49(1), 407-424.
  23. Liotta, L. A. (1992). Cancer cell invasion and metastasis. Scientific American, 266(2), 54-63.
  24. Khulpateea, B. R., Paulson, A., Carlson, M., Miller, D. S., & Lea, J. (2021). Stage IVA cervical cancer: outcomes of disease related complications and treatment. International Journal of Gynecological Cancer, 31(4), 518-523.
  25. Herzog, T. J., & Wright, J. D. (2007). The impact of cervical cancer on quality of life—the components and means for management. Gynecologic oncology, 107(3), 572-577.
  26. Pedersen, B., Koktved, D. P., & Nielsen, L. L. (2013). Living with side effects from cancer treatment–a challenge to target information. Scandinavian journal of caring sciences, 27(3), 715-723.
  27. Bodenheimer, T., & Berry-Millett, R. (2009). Care management of patients with complex health care needs. Policy, 1(6), 1-16.
  28. Haverkos, H., Rohrer, M., & Pickworth, W. (2000). The cause of invasive cervical cancer could be multifactorial. Biomedicine & pharmacotherapy, 54(1), 54-59.
  29. Goldstein, A., Gersh, M., Skovronsky, G., & Moss, C. (2024). The future of cervical cancer screening. International journal of women's health, 1715-1731.
  30. Sankaranarayanan, R., Nessa, A., Esmy, P. O., & Dangou, J. M. (2012). Visual inspection methods for cervical cancer prevention. Best practice & research Clinical obstetrics & gynaecology, 26(2), 221-232.
  31. Raju, K., Kukkamgai, H. M., & Kamarthi, P. P. (2025). Evolution of Cervical Cancer Screening Techniques: A Concept of Translation Medicine. Indian Journal of Surgical Oncology, 1-12.
  32. Castera, L. (2020). Non?invasive tests for liver fibrosis in NAFLD: creating pathways between primary healthcare and liver clinics. Liver International, 40, 77-81.
  33. Robera, D. (2023). Determinants Of Cryotherapy Utilization Among Cervical Cancer Screened Positive Women in Public Health Facilities of West Shoa Zone, Oromia, Ethiopia (Doctoral dissertation, Ambo University).
  34. Schiller, J. T., & Davies, P. (2004). Delivering on the promise: HPV vaccines and cervical cancer. Nature Reviews Microbiology, 2(4), 343-347.
  35. Tewari, K. S., & Monk, B. J. (2019). Evidence-based treatment paradigms for management of invasive cervical carcinoma. Journal of Clinical Oncology, 37(27), 2472-2489.
  36. Zafar, A., Khatoon, S., Khan, M. J., Abu, J., & Naeem, A. (2025). Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discover oncology, 16(1), 607.
  37. Marnitz, S., Martus, P., Köhler, C., Stromberger, C., Asse, E., Mallmann, P., ... & Budach, V. (2016). Role of surgical versus clinical staging in Chemoradiated FIGO stage IIB-IVA cervical cancer patients—acute toxicity and treatment quality of the uterus-11 Multicenter phase III intergroup trial of the German radiation oncology group and the gynecologic cancer group. International Journal of Radiation Oncology* Biology* Physics, 94(2), 243-253.
  38. Dasari, S., Njiki, S., Mbemi, A., Yedjou, C. G., & Tchounwou, P. B. (2022). Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. International journal of molecular sciences, 23(3), 1532.
  39. Williamson, C. W., Liu, H. C., Mayadev, J., & Mell, L. K. (2021). Advances in external beam radiation therapy and brachytherapy for cervical cancer. Clinical Oncology, 33(9), 567-578.
  40. Lin, Y., Chen, K., Lu, Z., Zhao, L., Tao, Y., Ouyang, Y., & Cao, X. (2018). Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis. Radiation Oncology, 13(1), 177.
  41. Hunt, A. (2022). Magnetic resonance guided radiotherapy for the treatment of bladder and pancreatic cancer.
  42. Evangelista, L., Panunzio, A., Polverosi, R., Ferretti, A., Chondrogiannis, S., Pomerri, F., ... & Muzzio, P. C. (2012). Early bone marrow metastasis detection: the additional value of FDG-PET/CT vs. CT imaging. Biomedicine & Pharmacotherapy, 66(6), 448-453.
  43. Khan, A. (2021). The value of elective pelvic lymph node radiotherapy in high risk prostate cancer.
  44. Anghel, B., Serboiu, C., Marinescu, A., Taciuc, I. A., Bobirca, F., & Stanescu, A. D. (2023). Recent advances and adaptive strategies in image guidance for cervical cancer radiotherapy. Medicina, 59(10), 1735.
  45. De Los Santos, J., Popple, R., Agazaryan, N., Bayouth, J. E., Bissonnette, J. P., Bucci, M. K., ... & Chetty, I. J. (2013). Image guided radiation therapy (IGRT) technologies for radiation therapy localization and delivery. International Journal of Radiation Oncology* Biology* Physics, 87(1), 33-45.
  46. Goyal, S., & Kataria, T. (2014). Image guidance in radiation therapy: techniques and applications. Radiology research and practice, 2014(1), 705604.
  47. Kagei, K., Tokuuye, K., Okumura, T., Ohara, K., Shioyama, Y., Sugahara, S., & Akine, Y. (2003). Long-term results of proton beam therapy for carcinoma of the uterine cervix. International Journal of Radiation Oncology* Biology* Physics, 55(5), 1265-1271.
  48. Moreno, A. C., Frank, S. J., Garden, A. S., Rosenthal, D. I., Fuller, C. D., Gunn, G. B., ... & Blanchard, P. (2019). Intensity modulated proton therapy (IMPT)–The future of IMRT for head and neck cancer. Oral oncology, 88, 66-74.
  49. Williamson, C. W., Liu, H. C., Mayadev, J., & Mell, L. K. (2021). Advances in external beam radiation therapy and brachytherapy for cervical cancer. Clinical Oncology, 33(9), 567-578.
  50. Badiyan, S. N., Hallemeier, C. L., Lin, S. H., Hall, M. D., & Chuong, M. D. (2018). Proton beam therapy for gastrointestinal cancers: past, present, and future. Journal of gastrointestinal oncology, 9(5), 962.
  51. Ahmed, R. S., Kim, R. Y., Duan, J., Meleth, S., De Los Santos, J. F., & Fiveash, J. B. (2004). IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. International Journal of Radiation Oncology* Biology* Physics, 60(2), 505-512.
  52. Rosenbrock, J., Baues, C., Vasquez-Torres, A., Clivio, A., Fogliata, A., Borchmann, P., ... & Cozzi, L. (2022). Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients. Acta Oncologica, 61(1), 81-88.
  53. Huang, Y., Qin, T., Yang, M., & Liu, Z. (2023). Impact of ovary-sparing treatment planning on plan quality, treatment time and gamma passing rates in intensity-modulated radiotherapy for stage I/II cervical cancer. Medicine, 102(50), e36373.
  54. Cheng, X., Liu, J., Lv, X., & Sun, L. (2025). Key Considerations for Ovarian Preservation during Radiotherapy for Cervical Carcinoma. Clinical and Experimental Obstetrics & Gynecology, 52(2), 26399.
  55. Taunk, N. (2022). The role of proton therapy in gynecological radiation oncology. International Journal of Gynecological Cancer, 32(3), 414-420.
  56. Viani, G. A., da Silva, L. B. G., da Silva, B. B., Crempe, Y. B., Martins, V. S., Ferrari, R. J. R., ... & Stefano, E. J. (2013). Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment. Radiation Oncology, 8(1), 94.
  57. Pollock, A. E., Remick, J. S., & Mohindra, P. (2022). Gynecologic Cancers. Principles and Practice of Particle Therapy, 425-444.
  58. Guimarães, Y. M., Godoy, L. R., Longatto-Filho, A., & Reis, R. D. (2022). Management of early-stage cervical cancer: a literature review. Cancers, 14(3), 575.
  59. Lee, S. W., Kim, Y. M., Son, W. S., You, H. J., Kim, D. Y., Kim, J. H., ... & Nam, J. H. (2009). The efficacy of conservative management after conization in patients with stage IA1 microinvasive cervical carcinoma. Acta Obstetricia et Gynecologica Scandinavica, 88(2), 209-215.
  60. Tsvetkova, D., & Ivanova, S. (2022). Application of approved cisplatin derivatives in combination therapy against different cancer diseases. Molecules, 27(8), 2466.
  61. Lee, H. S., & Park, S. W. (2016). Systemic chemotherapy in advanced pancreatic cancer. Gut and liver, 10(3), 340.
  62. Jyotirmayee, B., & Mahalik, G. (2022). A review on selected pharmacological activities of Curcuma longa L. International Journal of Food Properties, 25(1), 1377-1398.
  63. Abdullahi, H. M. (2024). In Vitro, In Silico and In Vivo Antidiabetic Properties of Ethanolic Extract of Momordica charantia Seed (Master's thesis, Kwara State University (Nigeria).
  64. Peng, Y., Ao, M., Dong, B., Jiang, Y., Yu, L., Chen, Z., ... & Xu, R. (2021). Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug design, development and therapy, 4503-4525.
  65. Ismail, N. I., Othman, I., Abas, F., H. Lajis, N., & Naidu, R. (2019). Mechanism of apoptosis induced by curcumin in colorectal cancer. International journal of molecular sciences, 20(10), 2454.
  66. Zhang, X., Chen, M., Zou, P., Kanchana, K., Weng, Q., Chen, W., ... & Liang, G. (2015). Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. BMC cancer, 15(1), 866.
  67. Mortezaee, K., Salehi, E., Mirtavoos?mahyari, H., Motevaseli, E., Najafi, M., Farhood, B., ... & Sahebkar, A. (2019). Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. Journal of cellular physiology, 234(8), 12537-12550.
  68. Tan, B. L., & Norhaizan, M. E. (2019). Curcumin combination chemotherapy: The implication and efficacy in cancer. Molecules, 24(14), 2527.
  69. Su, J. H., Wu, A., Scotney, E., Ma, B., Monie, A., Hung, C. F., & Wu, T. C. (2010). Immunotherapy for cervical cancer: Research status and clinical potential. BioDrugs, 24(2), 109-129.
  70. Stohs, S. J., Chen, O., Ray, S. D., Ji, J., Bucci, L. R., & Preuss, H. G. (2020). Highly bioavailable forms of curcumin and promising avenues for curcumin-based research and application: a review. Molecules, 25(6), 1397.
  71. Jacob, S., Kather, F. S., Morsy, M. A., Boddu, S. H., Attimarad, M., Shah, J., ... & Nair, A. B. (2024). Advances in nanocarrier systems for overcoming formulation challenges of curcumin: current insights. Nanomaterials, 14(8), 672.
  72. Teymouri, M., Pirro, M., Johnston, T. P., & Sahebkar, A. (2017). Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features. Biofactors, 43(3), 331-346.
  73. Zhang, X., Zhu, L., Wang, X., Zhang, H., Wang, L., & Xia, L. (2023). Basic research on curcumin in cervical cancer: Progress and perspectives. Biomedicine & Pharmacotherapy, 162, 114590.
  74. Dutta, R., Khalil, R., Green, R., Mohapatra, S. S., & Mohapatra, S. (2019). Withania somnifera (Ashwagandha) and withaferin A: Potential in integrative oncology. International journal of molecular sciences, 20(21), 5310.
  75. Umadevi, M., Rajeswari, R., Rahale, C. S., Selvavenkadesh, S., Pushpa, R., Kumar, K. S., & Bhowmik, D. (2012). Traditional and medicinal uses of Withania somnifera. The pharma innovation, 1(9, Part A), 102.
  76. Behl, T., Sharma, A., Sharma, L., Sehgal, A., Zengin, G., Brata, R., ... & Bungau, S. (2020). Exploring the multifaceted therapeutic potential of withaferin A and its derivatives. Biomedicines, 8(12), 571.
  77. Shenoy, P. S., Dash, S., Joshi, D., Rekhi, B., Gota, V., & Ray, P. (2025). Withaferin A Exerts Cytotoxicity in Single/Multidrug?Resistant Gastric and Ovarian Cancer Cells and Tumor Xenografts Through the AKT–NF?κB–STAT3–Survivin Axis. Molecular Carcinogenesis.
  78. Constantinou, A. I., Kamath, N., & Murley, J. S. (1998). Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. European Journal of Cancer, 34(12), 1927-1934.
  79. Sun, B., Lu, C., Zhou, G. P., & Xing, C. Y. (2011). Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress. Nephron Experimental Nephrology, 117(3), e53-e61.
  80. Dote, H., Burgan, W. E., Camphausen, K., & Tofilon, P. J. (2006). Inhibition of hsp90 compromises the DNA damage response to radiation. Cancer research, 66(18), 9211-9220.
  81. Shelke, G. V., Jagtap, J. C., Kim, D. K., Shah, R. D., Das, G., Shivayogi, M., ... & Shastry, P. (2017). TNF-α and IFN-γ together up-regulates par-4 expression and induce apoptosis in human neuroblastomas. Biomedicines, 6(1), 4.
  82. Henrique, T., Zanon, C. D. F., Girol, A. P., Stefanini, A. C. B., Contessoto, N. S. D. A., da Silveira, N. J., ... & Tajara, E. H. (2020). Biological and physical approaches on the role of piplartine (piperlongumine) in cancer. Scientific Reports, 10(1), 22283.
  83. Han, E. J., Choi, E. Y., Jeon, S. J., Lee, S. W., Moon, J. M., Jung, S. H., ... & Jung, J. Y. (2023). Piperlongumine induces apoptosis and autophagy via the PI3K/Akt/mTOR pathway in KB human cervical cancer cells. Food and Chemical Toxicology, 180, 114051.
  84. Wiraswati, H. L., Ma’ruf, I. F., Hidayati, N. A., Ramadhanti, J., Calina, D., & Sharifi-Rad, J. (2025). Harnessing the anticancer potential of Piper nigrum: a synergistic approach to chemotherapy enhancement and reduced side effects. Discover Oncology, 16(1), 10.
  85. Umapathy, V. R., Dhanavel, A., Kesavan, R., & Natarajan, P. M. (2024). Anticancer potential of the principal constituent of Piper nigrum, Piperine: a comprehensive review. Cureus, 16(2).
  86. Owa, T., Yoshino, H., Yoshimatsu, K., & Nagasu, T. (2001). Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Current medicinal chemistry, 8(12), 1487-1503.
  87. Zadorozhna, M., Tataranni, T., & Mangieri, D. (2019). Piperine: role in prevention and progression of cancer. Molecular biology reports, 46(5), 5617-5629.
  88. Nugroho, A. K., Kusumorini, N., Pramono, S., & Martien, R. (2023). An update on nanoparticle formulation design of piperine to improve its oral bioavailability: a review. Iraqi Journal of Pharmaceutical Sciences, 32(1), 14-30.
  89. Cardoso, L. P., de Sousa, S. O., Gusson-Zanetoni, J. P., de Melo Moreira Silva, L. L., Frigieri, B. M., Henrique, T., ... & Rodrigues-Lisoni, F. C. (2023). Piperine reduces neoplastic progression in cervical cancer cells by downregulating the cyclooxygenase 2 pathway. Pharmaceuticals, 16(1), 103.
  90. Song, P., Yu, X., Yang, W., & Wang, Q. (2021). Natural phytoalexin stilbene compound resveratrol and its derivatives as anti-tobacco mosaic virus and anti-phytopathogenic fungus agents. Scientific Reports, 11(1), 16509.
  91. Moga, M. A., Dimienescu, O. G., Arvatescu, C. A., Mironescu, A., Dracea, L., & Ples, L. (2016). The role of natural polyphenols in the prevention and treatment of cervical cancer—An overview. Molecules, 21(8), 1055.
  92. Thomas, E., Gopalakrishnan, V., Hegde, M., Kumar, S., Karki, S. S., Raghavan, S. C., & Choudhary, B. (2016). A novel resveratrol-based tubulin inhibitor induces mitotic arrest and activates apoptosis in cancer cells. Scientific reports, 6(1), 34653.
  93. Rauf, A., Imran, M., Butt, M. S., Nadeem, M., Peters, D. G., & Mubarak, M. S. (2018). Resveratrol as an anti-cancer agent: A review. Critical reviews in food science and nutrition, 58(9), 1428-1447.
  94. Paliwal, R., Paliwal, S. R., Kenwat, R., Kurmi, B. D., & Sahu, M. K. (2020). Solid lipid nanoparticles: A review on recent perspectives and patents. Expert opinion on therapeutic patents, 30(3), 179-194.
  95. He, M., Xia, L., & Li, J. (2021). Potential mechanisms of plant-derived natural products in the treatment of cervical cancer. Biomolecules, 11(10), 1539.
  96. Zhou, Y., Yang, Z. Y., & Tang, R. C. (2016). Bioactive and UV protective silk materials containing baicalin—The multifunctional plant extract from Scutellaria baicalensis Georgi. Materials Science and Engineering: C, 67, 336-344.
  97. Bie, B., Sun, J., Guo, Y., Li, J., Jiang, W., Yang, J., ... & Li, Z. (2017). Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma. Biomedicine & Pharmacotherapy, 93, 1285-1291.
  98. Chen, J., Li, Z., Chen, A. Y., Ye, X., Luo, H., Rankin, G. O., & Chen, Y. C. (2013). Inhibitory effect of baicalin and baicalein on ovarian cancer cells. International journal of molecular sciences, 14(3), 6012-6025.
  99. Wu, X., Yang, Z., Dang, H., Peng, H., & Dai, Z. (2018). Baicalein inhibits the proliferation of cervical cancer cells through the GSK3β-dependent pathway. Oncology Research, 26(4), 645.
  100. Bishop, K. S., Kao, C. H., Xu, Y., Glucina, M. P., Paterson, R. R. M., & Ferguson, L. R. (2015). From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry, 114, 56-65.
  101. Amara, K. (2017). In vitro production of Ganoderma lucidum mycelium from northeast Portugal: The antioxidant potential of tocopherols extract in the preservation of natural yogurt (Master's thesis, Instituto Politecnico de Braganca (Portugal).
  102. Nie, Z. J., Zhang, Y. G., Chang, Y. H., Li, Q. Y., & Zhang, Y. L. (2018). Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal transition through GLP-1R/sirt3 pathway. Biomedicine & Pharmacotherapy, 106, 1364-1369.
  103. Jin, H., Song, C., Zhao, Z., & Zhou, G. (2020). Ganoderma lucidum polysaccharide, an extract from ganoderma lucidum, exerts suppressive effect on cervical cancer cell malignancy through mitigating epithelial-mesenchymal and JAK/STAT5 signaling pathway. Pharmacology, 105(7-8), 461-470.
  104. Gao, X., & Homayoonfal, M. (2023). Exploring the anti-cancer potential of Ganoderma lucidum polysaccharides (GLPs) and their versatile role in enhancing drug delivery systems: a multifaceted approach to combat cancer. Cancer Cell International, 23(1), 324.
  105. Li, S., & Adair, K. T. (1994). XI SHU, a promising anti-tumor and anti-viral tree for the 21st century.
  106. Kamle, M., Pandhi, S., Mishra, S., Barua, S., Kurian, A., Mahato, D. K., ... & Sharifi-Rad, J. (2024). Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy. Medical Oncology, 41(11), 263.
  107. Percival, N. L. W., Nordin, A., & Fotopoulou, C. (2020). British Gynaecological Cancer Society (BGCS) Cervical Cancer Guidelines: Recommendations for Practice.
  108. Patel, R. R., He, K., Barsoumian, H. B., Chang, J. Y., Tang, C., Verma, V., ... & Welsh, J. W. (2021). High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: results of a phase II trial. Radiotherapy and Oncology, 162, 60-67.
  109. Kamle, M., Pandhi, S., Mishra, S., Barua, S., Kurian, A., Mahato, D. K., ... & Sharifi-Rad, J. (2024). Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy. Medical Oncology, 41(11), 263.
  110. Lee, C. Y., Yang, S. F., Wang, P. H., Su, C. W., Hsu, H. F., Tsai, H. T., & Hsiao, Y. H. (2019). Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein?9 and MAPK pathway. Environmental Toxicology, 34(1), 60-66.
  111. Su, C. W., Hsu, H. F., Lee, C. Y., Yang, S. F., Wang, P. H., Hsiao, Y. H., & Tsai, H. T. (2019). Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein?9 and MAPK pathway. Environmental Toxicology, 34(1).
  112. Majoumouo, M. S., Tincho, M. B., Kouipou Toghueo, R. M., Morris, T., Hiss, D. C., Boyom, F. F., & Mandal, C. (2020). Cytotoxicity potential of endophytic fungi extracts from Terminalia catappa against human cervical cancer cells. Journal of toxicology, 2020(1), 8871152.
  113. Chih, N. C. (2015). Antrodia camphorata. Medicinal Mushrooms-A Clinical Guide, 1843.
  114. Shukla, S., & Mehta, A. (2015). Anticancer potential of medicinal plants and their phytochemicals: a review. Brazilian Journal of Botany, 38(2), 199-210.
  115. Zhao, H., Li, J., Zhang, J., Wang, X., Liu, M., Zhang, C., & Jia, L. (2017). Hepatoprotective and in vitro antioxidant effects of native depolymerised-exopolysaccharides derived from Termitomyces albuminosus. Scientific Reports, 7(1), 3910.
  116. Yang, P. Y., Hu, D. N., & Liu, F. S. (2013). Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata. The American Journal of Chinese Medicine, 41(05), 1169-1180.
  117. Pan, J., Xu, G., & Yeung, S. C. J. (2001). Cytochrome c release is upstream to activation of caspase-9, caspase-8, and caspase-3 in the enhanced apoptosis of anaplastic thyroid cancer cells induced by manumycin and paclitaxel. The Journal of Clinical Endocrinology & Metabolism, 86(10), 4731-4740.
  118. Chota, A., George, B. P., & Abrahamse, H. (2021). Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death. Oncotarget, 12(16), 1615.
  119. Alshatwi, A. A., Athinarayanan, J., & Vaiyapuri Subbarayan, P. (2015). Green synthesis of platinum nanoparticles that induce cell death and G2/M-phase cell cycle arrest in human cervical cancer cells. Journal of Materials Science: Materials in Medicine, 26(1), 7.
  120. Yang, P. Y., Hu, D. N., Kao, Y. H., Lin, I., & Liu, F. S. (2018). Butein induces apoptotic cell death of human cervical cancer cells. Oncology Letters, 16(5), 6615-6623.
  121. Rodríguez-Berriguete, G., Galvis, L., Fraile, B., de Bethencourt, F. R., Martínez-Onsurbe, P., Olmedilla, G., ... & Royuela, M. (2012). Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors. Human pathology, 43(2), 229-237.
  122. Hsiao, Y. H., Lin, C. W., Wang, P. H., Hsin, M. C., & Yang, S. F. (2019). The potential of Chinese herbal medicines in the treatment of cervical cancer. Integrative Cancer Therapies, 18, 1534735419861693.
  123. Kaushik, A., Kaushik, M., Kaur, G., & Gupta, V. (2024). Perspective of secondary metabolites in respect of multidrug resistance (MDR): a review. Infectious Disorders-Drug TargetsDisorders), 24(4), 40-52.
  124. Peng, R., Xu, M., Xie, B., Min, Q., Hui, S., Du, Z., ... & Qin, S. (2023). Insights on antitumor activity and mechanism of natural benzophenanthridine alkaloids. Molecules, 28(18), 6588.
  125. Mazur, O., Ba?dysz, S., Warowicka, A., & Nawrot, R. (2022). Tap the sap–investigation of latex-bearing plants in the search of potential anticancer biopharmaceuticals. Frontiers in plant science, 13, 979678.
  126. Singh, S. P., Tiyasha, T., Negi, N., Bhagat, S. K., & Kumar, V. (2025). Integrated review of Myrica esculenta (bayberry) in therapeutic nutritional and environmental contexts. Discover Food, 5(1), 253.
  127. Pathak, S., Banerjee, A., & Khuda-Bukhsh, A. (2010). Efficacy of ethanolic spore extract of Lycopodium clavatum in reducing induced hepatotoxicity and genotoxicity in mice. International Journal of Biological and Chemical Sciences, 4(3).
  128. Mandal, S. K., Biswas, R., Bhattacharyya, S. S., Paul, S., Dutta, S., Pathak, S., & Khuda-Bukhsh, A. R. (2010). Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. European Journal of Pharmacology, 626(2-3), 115-122.  

Reference

  1. Hull, R., Mbele, M., Makhafola, T., Hicks, C., Wang, S. M., Reis, R. M., ... & Dlamini, Z. (2020). Cervical cancer in low and middle income countries. Oncology letters, 20(3), 2058-2074.
  2. Sreedevi, A., Javed, R., & Dinesh, A. (2015). Epidemiology of cervical cancer with special focus on India. International journal of women's health, 405-414.
  3. Sharma, N., Upadhyay, S., Gupta, P. C., & Katiyar, P. (2024). Cervical Cancer: Basic Information and Comprehensive Control. In Women's Health: A Comprehensive Guide to Common Health Issues in Women (pp. 129-158). Bentham Science Publishers.
  4. Arango-Bravo, E. A., del Carmen Cetina-Perez, L., Galicia-Carmona, T., Castro-Eguiluz, D., Gallardo-Rincon, D., Cruz-Bautista, I., & Duenas-Gonzalez, A. (2022). The health system and  access to treatment in patients with cervical cancer in Mexico. Frontiers in Oncology, 12, 1028291.
  5. Prat, J. (2015). Pathology of cancers of the female genital tract. International Journal of Gynecology & Obstetrics, 131, S132-S145.
  6. Omotoso, O., Teibo, J. O., Atiba, F. A., Oladimeji, T., Paimo, O. K., Ataya, F. S., ... & Alexiou, A. (2023). Addressing cancer care inequities in sub-Saharan Africa: current challenges and proposed solutions. International Journal for Equity in Health, 22(1), 189.
  7. Togashi, K., Morikawa, K., Kataoka, M. L., & Konishi, J. (1998). Cervical cancer. Journal of Magnetic Resonance Imaging, 8(2), 391-397.
  8. Singh, D., Vignat, J., Lorenzoni, V., Eslahi, M., Ginsburg, O., Lauby-Secretan, B., ... & Vaccarella, S. (2023). Global estimates of incidence and mortality of cervical cancer in 2020: a baseline analysis of the WHO Global Cervical Cancer Elimination Initiative. The lancet global health, 11(2), e197-e206.
  9. Ramakrishnan, S., Partricia, S., & Mathan, G. (2015). Overview of high-risk HPV's 16 and 18 infected cervical cancer: pathogenesis to prevention. Biomedicine & pharmacotherapy, 70, 103-110.
  10. Tsikouras, P., Zervoudis, S., Manav, B., Tomara, E., Iatrakis, G., Romanidis, C., ... & Galazios, G. (2016). Cervical cancer: screening, diagnosis and staging. J buon, 21(2), 320-325.
  11. Li, X., Jiang, S., & Tapping, R. I. (2010). Toll-like receptor signaling in cell proliferation and survival. Cytokine, 49(1), 1-9.
  12. Hartman, M. L., & Czyz, M. (2020). BCL-w: apoptotic and non-apoptotic role in health and disease. Cell Death & Disease, 11(4), 260.
  13. Vimalraj, S. (2022). A concise review of VEGF, PDGF, FGF, Notch, angiopoietin, and HGF signalling in tumor angiogenesis with a focus on alternative approaches and future directions. International Journal of Biological Macromolecules, 221, 1428-1438.
  14. Martinezi, A. G., Kumar, P. S., Hernandez-Kapila, Y. L., & Ambalavanan, N. (2024). Pathology and management of periodontal problems associated with viral infection, including HIV, COVID, and Others. Newman and Carranza's Clinical Periodontology: 4th South Asia Edition-E-Book, 267.
  15. Johnson, K. M., Kines, R. C., Roberts, J. N., Lowy, D. R., Schiller, J. T., & Day, P. M. (2009). Role of heparan sulfate in attachment to and infection of the murine female genital tract by human papillomavirus. Journal of virology, 83(5), 2067-2074.
  16. Swindle, C. S., Zou, N., Van Tine, B. A., Shaw, G. M., Engler, J. A., & Chow, L. T. (1999). Human papillomavirus DNA replication compartments in a transient DNA replication system. Journal of virology, 73(2), 1001-1009.
  17. Chiang, C. M., Ustav, M., Stenlund, A., Ho, T. F., Broker, T. R., & Chow, L. T. (1992). Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proceedings of the National Academy of Sciences, 89(13), 5799-5803.
  18. Li, J., & Li, S. (2025). From Viral Infection to Genome Reshaping: The Triggering Role of HPV Integration in Cervical Cancer. International Journal of Molecular Sciences, 26(18), 9214.
  19. Vousden, K. (1993). Interactions of human papillomavirus transforming proteins with the products of tumor suppressor genes. The FASEB journal, 7(10), 872-879.
  20. Steinbach, A., & Riemer, A. B. (2018). Immune evasion mechanisms of human papillomavirus: An update. International journal of cancer, 142(2), 224-229.
  21. Bubeník, J. (2003). Tumour MHC class I downregulation and immunotherapy. Oncology reports, 10(6), 2005-2008.
  22. Zetter, B. R. (1998). Angiogenesis and tumor metastasis. Annual review of medicine, 49(1), 407-424.
  23. Liotta, L. A. (1992). Cancer cell invasion and metastasis. Scientific American, 266(2), 54-63.
  24. Khulpateea, B. R., Paulson, A., Carlson, M., Miller, D. S., & Lea, J. (2021). Stage IVA cervical cancer: outcomes of disease related complications and treatment. International Journal of Gynecological Cancer, 31(4), 518-523.
  25. Herzog, T. J., & Wright, J. D. (2007). The impact of cervical cancer on quality of life—the components and means for management. Gynecologic oncology, 107(3), 572-577.
  26. Pedersen, B., Koktved, D. P., & Nielsen, L. L. (2013). Living with side effects from cancer treatment–a challenge to target information. Scandinavian journal of caring sciences, 27(3), 715-723.
  27. Bodenheimer, T., & Berry-Millett, R. (2009). Care management of patients with complex health care needs. Policy, 1(6), 1-16.
  28. Haverkos, H., Rohrer, M., & Pickworth, W. (2000). The cause of invasive cervical cancer could be multifactorial. Biomedicine & pharmacotherapy, 54(1), 54-59.
  29. Goldstein, A., Gersh, M., Skovronsky, G., & Moss, C. (2024). The future of cervical cancer screening. International journal of women's health, 1715-1731.
  30. Sankaranarayanan, R., Nessa, A., Esmy, P. O., & Dangou, J. M. (2012). Visual inspection methods for cervical cancer prevention. Best practice & research Clinical obstetrics & gynaecology, 26(2), 221-232.
  31. Raju, K., Kukkamgai, H. M., & Kamarthi, P. P. (2025). Evolution of Cervical Cancer Screening Techniques: A Concept of Translation Medicine. Indian Journal of Surgical Oncology, 1-12.
  32. Castera, L. (2020). Non?invasive tests for liver fibrosis in NAFLD: creating pathways between primary healthcare and liver clinics. Liver International, 40, 77-81.
  33. Robera, D. (2023). Determinants Of Cryotherapy Utilization Among Cervical Cancer Screened Positive Women in Public Health Facilities of West Shoa Zone, Oromia, Ethiopia (Doctoral dissertation, Ambo University).
  34. Schiller, J. T., & Davies, P. (2004). Delivering on the promise: HPV vaccines and cervical cancer. Nature Reviews Microbiology, 2(4), 343-347.
  35. Tewari, K. S., & Monk, B. J. (2019). Evidence-based treatment paradigms for management of invasive cervical carcinoma. Journal of Clinical Oncology, 37(27), 2472-2489.
  36. Zafar, A., Khatoon, S., Khan, M. J., Abu, J., & Naeem, A. (2025). Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy. Discover oncology, 16(1), 607.
  37. Marnitz, S., Martus, P., Köhler, C., Stromberger, C., Asse, E., Mallmann, P., ... & Budach, V. (2016). Role of surgical versus clinical staging in Chemoradiated FIGO stage IIB-IVA cervical cancer patients—acute toxicity and treatment quality of the uterus-11 Multicenter phase III intergroup trial of the German radiation oncology group and the gynecologic cancer group. International Journal of Radiation Oncology* Biology* Physics, 94(2), 243-253.
  38. Dasari, S., Njiki, S., Mbemi, A., Yedjou, C. G., & Tchounwou, P. B. (2022). Pharmacological effects of cisplatin combination with natural products in cancer chemotherapy. International journal of molecular sciences, 23(3), 1532.
  39. Williamson, C. W., Liu, H. C., Mayadev, J., & Mell, L. K. (2021). Advances in external beam radiation therapy and brachytherapy for cervical cancer. Clinical Oncology, 33(9), 567-578.
  40. Lin, Y., Chen, K., Lu, Z., Zhao, L., Tao, Y., Ouyang, Y., & Cao, X. (2018). Intensity-modulated radiation therapy for definitive treatment of cervical cancer: a meta-analysis. Radiation Oncology, 13(1), 177.
  41. Hunt, A. (2022). Magnetic resonance guided radiotherapy for the treatment of bladder and pancreatic cancer.
  42. Evangelista, L., Panunzio, A., Polverosi, R., Ferretti, A., Chondrogiannis, S., Pomerri, F., ... & Muzzio, P. C. (2012). Early bone marrow metastasis detection: the additional value of FDG-PET/CT vs. CT imaging. Biomedicine & Pharmacotherapy, 66(6), 448-453.
  43. Khan, A. (2021). The value of elective pelvic lymph node radiotherapy in high risk prostate cancer.
  44. Anghel, B., Serboiu, C., Marinescu, A., Taciuc, I. A., Bobirca, F., & Stanescu, A. D. (2023). Recent advances and adaptive strategies in image guidance for cervical cancer radiotherapy. Medicina, 59(10), 1735.
  45. De Los Santos, J., Popple, R., Agazaryan, N., Bayouth, J. E., Bissonnette, J. P., Bucci, M. K., ... & Chetty, I. J. (2013). Image guided radiation therapy (IGRT) technologies for radiation therapy localization and delivery. International Journal of Radiation Oncology* Biology* Physics, 87(1), 33-45.
  46. Goyal, S., & Kataria, T. (2014). Image guidance in radiation therapy: techniques and applications. Radiology research and practice, 2014(1), 705604.
  47. Kagei, K., Tokuuye, K., Okumura, T., Ohara, K., Shioyama, Y., Sugahara, S., & Akine, Y. (2003). Long-term results of proton beam therapy for carcinoma of the uterine cervix. International Journal of Radiation Oncology* Biology* Physics, 55(5), 1265-1271.
  48. Moreno, A. C., Frank, S. J., Garden, A. S., Rosenthal, D. I., Fuller, C. D., Gunn, G. B., ... & Blanchard, P. (2019). Intensity modulated proton therapy (IMPT)–The future of IMRT for head and neck cancer. Oral oncology, 88, 66-74.
  49. Williamson, C. W., Liu, H. C., Mayadev, J., & Mell, L. K. (2021). Advances in external beam radiation therapy and brachytherapy for cervical cancer. Clinical Oncology, 33(9), 567-578.
  50. Badiyan, S. N., Hallemeier, C. L., Lin, S. H., Hall, M. D., & Chuong, M. D. (2018). Proton beam therapy for gastrointestinal cancers: past, present, and future. Journal of gastrointestinal oncology, 9(5), 962.
  51. Ahmed, R. S., Kim, R. Y., Duan, J., Meleth, S., De Los Santos, J. F., & Fiveash, J. B. (2004). IMRT dose escalation for positive para-aortic lymph nodes in patients with locally advanced cervical cancer while reducing dose to bone marrow and other organs at risk. International Journal of Radiation Oncology* Biology* Physics, 60(2), 505-512.
  52. Rosenbrock, J., Baues, C., Vasquez-Torres, A., Clivio, A., Fogliata, A., Borchmann, P., ... & Cozzi, L. (2022). Volumetric modulated arc therapy versus intensity-modulated proton therapy in the irradiation of infra diaphragmatic Hodgkin Lymphoma in female patients. Acta Oncologica, 61(1), 81-88.
  53. Huang, Y., Qin, T., Yang, M., & Liu, Z. (2023). Impact of ovary-sparing treatment planning on plan quality, treatment time and gamma passing rates in intensity-modulated radiotherapy for stage I/II cervical cancer. Medicine, 102(50), e36373.
  54. Cheng, X., Liu, J., Lv, X., & Sun, L. (2025). Key Considerations for Ovarian Preservation during Radiotherapy for Cervical Carcinoma. Clinical and Experimental Obstetrics & Gynecology, 52(2), 26399.
  55. Taunk, N. (2022). The role of proton therapy in gynecological radiation oncology. International Journal of Gynecological Cancer, 32(3), 414-420.
  56. Viani, G. A., da Silva, L. B. G., da Silva, B. B., Crempe, Y. B., Martins, V. S., Ferrari, R. J. R., ... & Stefano, E. J. (2013). Acute toxicity profile in prostate cancer with conventional and hypofractionated treatment. Radiation Oncology, 8(1), 94.
  57. Pollock, A. E., Remick, J. S., & Mohindra, P. (2022). Gynecologic Cancers. Principles and Practice of Particle Therapy, 425-444.
  58. Guimarães, Y. M., Godoy, L. R., Longatto-Filho, A., & Reis, R. D. (2022). Management of early-stage cervical cancer: a literature review. Cancers, 14(3), 575.
  59. Lee, S. W., Kim, Y. M., Son, W. S., You, H. J., Kim, D. Y., Kim, J. H., ... & Nam, J. H. (2009). The efficacy of conservative management after conization in patients with stage IA1 microinvasive cervical carcinoma. Acta Obstetricia et Gynecologica Scandinavica, 88(2), 209-215.
  60. Tsvetkova, D., & Ivanova, S. (2022). Application of approved cisplatin derivatives in combination therapy against different cancer diseases. Molecules, 27(8), 2466.
  61. Lee, H. S., & Park, S. W. (2016). Systemic chemotherapy in advanced pancreatic cancer. Gut and liver, 10(3), 340.
  62. Jyotirmayee, B., & Mahalik, G. (2022). A review on selected pharmacological activities of Curcuma longa L. International Journal of Food Properties, 25(1), 1377-1398.
  63. Abdullahi, H. M. (2024). In Vitro, In Silico and In Vivo Antidiabetic Properties of Ethanolic Extract of Momordica charantia Seed (Master's thesis, Kwara State University (Nigeria).
  64. Peng, Y., Ao, M., Dong, B., Jiang, Y., Yu, L., Chen, Z., ... & Xu, R. (2021). Anti-inflammatory effects of curcumin in the inflammatory diseases: status, limitations and countermeasures. Drug design, development and therapy, 4503-4525.
  65. Ismail, N. I., Othman, I., Abas, F., H. Lajis, N., & Naidu, R. (2019). Mechanism of apoptosis induced by curcumin in colorectal cancer. International journal of molecular sciences, 20(10), 2454.
  66. Zhang, X., Chen, M., Zou, P., Kanchana, K., Weng, Q., Chen, W., ... & Liang, G. (2015). Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells. BMC cancer, 15(1), 866.
  67. Mortezaee, K., Salehi, E., Mirtavoos?mahyari, H., Motevaseli, E., Najafi, M., Farhood, B., ... & Sahebkar, A. (2019). Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy. Journal of cellular physiology, 234(8), 12537-12550.
  68. Tan, B. L., & Norhaizan, M. E. (2019). Curcumin combination chemotherapy: The implication and efficacy in cancer. Molecules, 24(14), 2527.
  69. Su, J. H., Wu, A., Scotney, E., Ma, B., Monie, A., Hung, C. F., & Wu, T. C. (2010). Immunotherapy for cervical cancer: Research status and clinical potential. BioDrugs, 24(2), 109-129.
  70. Stohs, S. J., Chen, O., Ray, S. D., Ji, J., Bucci, L. R., & Preuss, H. G. (2020). Highly bioavailable forms of curcumin and promising avenues for curcumin-based research and application: a review. Molecules, 25(6), 1397.
  71. Jacob, S., Kather, F. S., Morsy, M. A., Boddu, S. H., Attimarad, M., Shah, J., ... & Nair, A. B. (2024). Advances in nanocarrier systems for overcoming formulation challenges of curcumin: current insights. Nanomaterials, 14(8), 672.
  72. Teymouri, M., Pirro, M., Johnston, T. P., & Sahebkar, A. (2017). Curcumin as a multifaceted compound against human papilloma virus infection and cervical cancers: A review of chemistry, cellular, molecular, and preclinical features. Biofactors, 43(3), 331-346.
  73. Zhang, X., Zhu, L., Wang, X., Zhang, H., Wang, L., & Xia, L. (2023). Basic research on curcumin in cervical cancer: Progress and perspectives. Biomedicine & Pharmacotherapy, 162, 114590.
  74. Dutta, R., Khalil, R., Green, R., Mohapatra, S. S., & Mohapatra, S. (2019). Withania somnifera (Ashwagandha) and withaferin A: Potential in integrative oncology. International journal of molecular sciences, 20(21), 5310.
  75. Umadevi, M., Rajeswari, R., Rahale, C. S., Selvavenkadesh, S., Pushpa, R., Kumar, K. S., & Bhowmik, D. (2012). Traditional and medicinal uses of Withania somnifera. The pharma innovation, 1(9, Part A), 102.
  76. Behl, T., Sharma, A., Sharma, L., Sehgal, A., Zengin, G., Brata, R., ... & Bungau, S. (2020). Exploring the multifaceted therapeutic potential of withaferin A and its derivatives. Biomedicines, 8(12), 571.
  77. Shenoy, P. S., Dash, S., Joshi, D., Rekhi, B., Gota, V., & Ray, P. (2025). Withaferin A Exerts Cytotoxicity in Single/Multidrug?Resistant Gastric and Ovarian Cancer Cells and Tumor Xenografts Through the AKT–NF?κB–STAT3–Survivin Axis. Molecular Carcinogenesis.
  78. Constantinou, A. I., Kamath, N., & Murley, J. S. (1998). Genistein inactivates bcl-2, delays the G2/M phase of the cell cycle, and induces apoptosis of human breast adenocarcinoma MCF-7 cells. European Journal of Cancer, 34(12), 1927-1934.
  79. Sun, B., Lu, C., Zhou, G. P., & Xing, C. Y. (2011). Suppression of Par-4 protects human renal proximal tubule cells from apoptosis induced by oxidative stress. Nephron Experimental Nephrology, 117(3), e53-e61.
  80. Dote, H., Burgan, W. E., Camphausen, K., & Tofilon, P. J. (2006). Inhibition of hsp90 compromises the DNA damage response to radiation. Cancer research, 66(18), 9211-9220.
  81. Shelke, G. V., Jagtap, J. C., Kim, D. K., Shah, R. D., Das, G., Shivayogi, M., ... & Shastry, P. (2017). TNF-α and IFN-γ together up-regulates par-4 expression and induce apoptosis in human neuroblastomas. Biomedicines, 6(1), 4.
  82. Henrique, T., Zanon, C. D. F., Girol, A. P., Stefanini, A. C. B., Contessoto, N. S. D. A., da Silveira, N. J., ... & Tajara, E. H. (2020). Biological and physical approaches on the role of piplartine (piperlongumine) in cancer. Scientific Reports, 10(1), 22283.
  83. Han, E. J., Choi, E. Y., Jeon, S. J., Lee, S. W., Moon, J. M., Jung, S. H., ... & Jung, J. Y. (2023). Piperlongumine induces apoptosis and autophagy via the PI3K/Akt/mTOR pathway in KB human cervical cancer cells. Food and Chemical Toxicology, 180, 114051.
  84. Wiraswati, H. L., Ma’ruf, I. F., Hidayati, N. A., Ramadhanti, J., Calina, D., & Sharifi-Rad, J. (2025). Harnessing the anticancer potential of Piper nigrum: a synergistic approach to chemotherapy enhancement and reduced side effects. Discover Oncology, 16(1), 10.
  85. Umapathy, V. R., Dhanavel, A., Kesavan, R., & Natarajan, P. M. (2024). Anticancer potential of the principal constituent of Piper nigrum, Piperine: a comprehensive review. Cureus, 16(2).
  86. Owa, T., Yoshino, H., Yoshimatsu, K., & Nagasu, T. (2001). Cell cycle regulation in the G1 phase: a promising target for the development of new chemotherapeutic anticancer agents. Current medicinal chemistry, 8(12), 1487-1503.
  87. Zadorozhna, M., Tataranni, T., & Mangieri, D. (2019). Piperine: role in prevention and progression of cancer. Molecular biology reports, 46(5), 5617-5629.
  88. Nugroho, A. K., Kusumorini, N., Pramono, S., & Martien, R. (2023). An update on nanoparticle formulation design of piperine to improve its oral bioavailability: a review. Iraqi Journal of Pharmaceutical Sciences, 32(1), 14-30.
  89. Cardoso, L. P., de Sousa, S. O., Gusson-Zanetoni, J. P., de Melo Moreira Silva, L. L., Frigieri, B. M., Henrique, T., ... & Rodrigues-Lisoni, F. C. (2023). Piperine reduces neoplastic progression in cervical cancer cells by downregulating the cyclooxygenase 2 pathway. Pharmaceuticals, 16(1), 103.
  90. Song, P., Yu, X., Yang, W., & Wang, Q. (2021). Natural phytoalexin stilbene compound resveratrol and its derivatives as anti-tobacco mosaic virus and anti-phytopathogenic fungus agents. Scientific Reports, 11(1), 16509.
  91. Moga, M. A., Dimienescu, O. G., Arvatescu, C. A., Mironescu, A., Dracea, L., & Ples, L. (2016). The role of natural polyphenols in the prevention and treatment of cervical cancer—An overview. Molecules, 21(8), 1055.
  92. Thomas, E., Gopalakrishnan, V., Hegde, M., Kumar, S., Karki, S. S., Raghavan, S. C., & Choudhary, B. (2016). A novel resveratrol-based tubulin inhibitor induces mitotic arrest and activates apoptosis in cancer cells. Scientific reports, 6(1), 34653.
  93. Rauf, A., Imran, M., Butt, M. S., Nadeem, M., Peters, D. G., & Mubarak, M. S. (2018). Resveratrol as an anti-cancer agent: A review. Critical reviews in food science and nutrition, 58(9), 1428-1447.
  94. Paliwal, R., Paliwal, S. R., Kenwat, R., Kurmi, B. D., & Sahu, M. K. (2020). Solid lipid nanoparticles: A review on recent perspectives and patents. Expert opinion on therapeutic patents, 30(3), 179-194.
  95. He, M., Xia, L., & Li, J. (2021). Potential mechanisms of plant-derived natural products in the treatment of cervical cancer. Biomolecules, 11(10), 1539.
  96. Zhou, Y., Yang, Z. Y., & Tang, R. C. (2016). Bioactive and UV protective silk materials containing baicalin—The multifunctional plant extract from Scutellaria baicalensis Georgi. Materials Science and Engineering: C, 67, 336-344.
  97. Bie, B., Sun, J., Guo, Y., Li, J., Jiang, W., Yang, J., ... & Li, Z. (2017). Baicalein: A review of its anti-cancer effects and mechanisms in Hepatocellular Carcinoma. Biomedicine & Pharmacotherapy, 93, 1285-1291.
  98. Chen, J., Li, Z., Chen, A. Y., Ye, X., Luo, H., Rankin, G. O., & Chen, Y. C. (2013). Inhibitory effect of baicalin and baicalein on ovarian cancer cells. International journal of molecular sciences, 14(3), 6012-6025.
  99. Wu, X., Yang, Z., Dang, H., Peng, H., & Dai, Z. (2018). Baicalein inhibits the proliferation of cervical cancer cells through the GSK3β-dependent pathway. Oncology Research, 26(4), 645.
  100. Bishop, K. S., Kao, C. H., Xu, Y., Glucina, M. P., Paterson, R. R. M., & Ferguson, L. R. (2015). From 2000 years of Ganoderma lucidum to recent developments in nutraceuticals. Phytochemistry, 114, 56-65.
  101. Amara, K. (2017). In vitro production of Ganoderma lucidum mycelium from northeast Portugal: The antioxidant potential of tocopherols extract in the preservation of natural yogurt (Master's thesis, Instituto Politecnico de Braganca (Portugal).
  102. Nie, Z. J., Zhang, Y. G., Chang, Y. H., Li, Q. Y., & Zhang, Y. L. (2018). Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal transition through GLP-1R/sirt3 pathway. Biomedicine & Pharmacotherapy, 106, 1364-1369.
  103. Jin, H., Song, C., Zhao, Z., & Zhou, G. (2020). Ganoderma lucidum polysaccharide, an extract from ganoderma lucidum, exerts suppressive effect on cervical cancer cell malignancy through mitigating epithelial-mesenchymal and JAK/STAT5 signaling pathway. Pharmacology, 105(7-8), 461-470.
  104. Gao, X., & Homayoonfal, M. (2023). Exploring the anti-cancer potential of Ganoderma lucidum polysaccharides (GLPs) and their versatile role in enhancing drug delivery systems: a multifaceted approach to combat cancer. Cancer Cell International, 23(1), 324.
  105. Li, S., & Adair, K. T. (1994). XI SHU, a promising anti-tumor and anti-viral tree for the 21st century.
  106. Kamle, M., Pandhi, S., Mishra, S., Barua, S., Kurian, A., Mahato, D. K., ... & Sharifi-Rad, J. (2024). Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy. Medical Oncology, 41(11), 263.
  107. Percival, N. L. W., Nordin, A., & Fotopoulou, C. (2020). British Gynaecological Cancer Society (BGCS) Cervical Cancer Guidelines: Recommendations for Practice.
  108. Patel, R. R., He, K., Barsoumian, H. B., Chang, J. Y., Tang, C., Verma, V., ... & Welsh, J. W. (2021). High-dose irradiation in combination with non-ablative low-dose radiation to treat metastatic disease after progression on immunotherapy: results of a phase II trial. Radiotherapy and Oncology, 162, 60-67.
  109. Kamle, M., Pandhi, S., Mishra, S., Barua, S., Kurian, A., Mahato, D. K., ... & Sharifi-Rad, J. (2024). Camptothecin and its derivatives: Advancements, mechanisms and clinical potential in cancer therapy. Medical Oncology, 41(11), 263.
  110. Lee, C. Y., Yang, S. F., Wang, P. H., Su, C. W., Hsu, H. F., Tsai, H. T., & Hsiao, Y. H. (2019). Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein?9 and MAPK pathway. Environmental Toxicology, 34(1), 60-66.
  111. Su, C. W., Hsu, H. F., Lee, C. Y., Yang, S. F., Wang, P. H., Hsiao, Y. H., & Tsai, H. T. (2019). Antimetastatic effects of Terminalia catappa leaf extracts on cervical cancer through the inhibition of matrix metalloprotein?9 and MAPK pathway. Environmental Toxicology, 34(1).
  112. Majoumouo, M. S., Tincho, M. B., Kouipou Toghueo, R. M., Morris, T., Hiss, D. C., Boyom, F. F., & Mandal, C. (2020). Cytotoxicity potential of endophytic fungi extracts from Terminalia catappa against human cervical cancer cells. Journal of toxicology, 2020(1), 8871152.
  113. Chih, N. C. (2015). Antrodia camphorata. Medicinal Mushrooms-A Clinical Guide, 1843.
  114. Shukla, S., & Mehta, A. (2015). Anticancer potential of medicinal plants and their phytochemicals: a review. Brazilian Journal of Botany, 38(2), 199-210.
  115. Zhao, H., Li, J., Zhang, J., Wang, X., Liu, M., Zhang, C., & Jia, L. (2017). Hepatoprotective and in vitro antioxidant effects of native depolymerised-exopolysaccharides derived from Termitomyces albuminosus. Scientific Reports, 7(1), 3910.
  116. Yang, P. Y., Hu, D. N., & Liu, F. S. (2013). Cytotoxic effect and induction of apoptosis in human cervical cancer cells by Antrodia camphorata. The American Journal of Chinese Medicine, 41(05), 1169-1180.
  117. Pan, J., Xu, G., & Yeung, S. C. J. (2001). Cytochrome c release is upstream to activation of caspase-9, caspase-8, and caspase-3 in the enhanced apoptosis of anaplastic thyroid cancer cells induced by manumycin and paclitaxel. The Journal of Clinical Endocrinology & Metabolism, 86(10), 4731-4740.
  118. Chota, A., George, B. P., & Abrahamse, H. (2021). Interactions of multidomain pro-apoptotic and anti-apoptotic proteins in cancer cell death. Oncotarget, 12(16), 1615.
  119. Alshatwi, A. A., Athinarayanan, J., & Vaiyapuri Subbarayan, P. (2015). Green synthesis of platinum nanoparticles that induce cell death and G2/M-phase cell cycle arrest in human cervical cancer cells. Journal of Materials Science: Materials in Medicine, 26(1), 7.
  120. Yang, P. Y., Hu, D. N., Kao, Y. H., Lin, I., & Liu, F. S. (2018). Butein induces apoptotic cell death of human cervical cancer cells. Oncology Letters, 16(5), 6615-6623.
  121. Rodríguez-Berriguete, G., Galvis, L., Fraile, B., de Bethencourt, F. R., Martínez-Onsurbe, P., Olmedilla, G., ... & Royuela, M. (2012). Immunoreactivity to caspase-3, caspase-7, caspase-8, and caspase-9 forms is frequently lost in human prostate tumors. Human pathology, 43(2), 229-237.
  122. Hsiao, Y. H., Lin, C. W., Wang, P. H., Hsin, M. C., & Yang, S. F. (2019). The potential of Chinese herbal medicines in the treatment of cervical cancer. Integrative Cancer Therapies, 18, 1534735419861693.
  123. Kaushik, A., Kaushik, M., Kaur, G., & Gupta, V. (2024). Perspective of secondary metabolites in respect of multidrug resistance (MDR): a review. Infectious Disorders-Drug TargetsDisorders), 24(4), 40-52.
  124. Peng, R., Xu, M., Xie, B., Min, Q., Hui, S., Du, Z., ... & Qin, S. (2023). Insights on antitumor activity and mechanism of natural benzophenanthridine alkaloids. Molecules, 28(18), 6588.
  125. Mazur, O., Ba?dysz, S., Warowicka, A., & Nawrot, R. (2022). Tap the sap–investigation of latex-bearing plants in the search of potential anticancer biopharmaceuticals. Frontiers in plant science, 13, 979678.
  126. Singh, S. P., Tiyasha, T., Negi, N., Bhagat, S. K., & Kumar, V. (2025). Integrated review of Myrica esculenta (bayberry) in therapeutic nutritional and environmental contexts. Discover Food, 5(1), 253.
  127. Pathak, S., Banerjee, A., & Khuda-Bukhsh, A. (2010). Efficacy of ethanolic spore extract of Lycopodium clavatum in reducing induced hepatotoxicity and genotoxicity in mice. International Journal of Biological and Chemical Sciences, 4(3).
  128. Mandal, S. K., Biswas, R., Bhattacharyya, S. S., Paul, S., Dutta, S., Pathak, S., & Khuda-Bukhsh, A. R. (2010). Lycopodine from Lycopodium clavatum extract inhibits proliferation of HeLa cells through induction of apoptosis via caspase-3 activation. European Journal of Pharmacology, 626(2-3), 115-122.  

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Dr. Pravin Kumar
Corresponding author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Sakshi
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Dr. Vinay Pandit
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Dr. M. S. Ashwat
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Dr. Mayank Sharma
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Dr. Swati Rana
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

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Pratibha Chaudhary
Co-author

Laureate Institute of Pharmacy, Kathog, Jawalamukhi, Himachal Pradesh, India

Sakshi, Dr. Pravin Kumar, Dr. Vinay Pandit, Dr. M. S. Ashwat, Dr. Mayank Sharma, Dr. Swati Rana, Pratibha Chaudhary, A Comprehensive Review of Herbal Therapeutics in Cervical Cancer: Bioactive Plant Compounds and their Anticancer Mechanisms, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 1, 1850-1870. https://doi.org/10.5281/zenodo.18300392

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