Gopeshwar Narayan

Background: Telomerase reactivation via hTERT upregulation drives cervical cancer progression, yet the epigenetic mechanisms remain poorly understood, particularly in India’s high-burden population. The TERT Hypermethylated Oncological Region (THOR) critically regulates hTERT transcription, but its functional role and clinical relevance are unexplored. Methods: We analyzed hTERT expression, telomere length, THOR methylation, and HPV status in 100 cervical cancer and 50 control tissues. Functional validation employed 5-aza-2′-deoxycytidine (AZA) treatment in C-33 A, ME-180, HeLa, SiHa, and Saos-2 cells, with menin recruitment assessed by ChIP assays. Results: hTERT expression and telomere length significantly elevated in cervical cancer, correlating with age, International Federation of Gynecology and Obstetrics (FIGO) stage, and menopausal status. THOR hypermethylation emerged as an independent epigenetic regulator of hTERT, operating regardless of clinicopathological parameters. Strikingly, HPV status showed no association with hTERT, telomere length, or THOR methylation, revealing HPV-independent epigenetic drivers. AZA treatment partially reversed hTERT upregulation and suppressed telomerase activity with cell line-specific responses. Menin enrichment was markedly reduced at hypermethylated THOR but restored upon hypomethylation, establishing a direct epigenetic-mechanistic link. Conclusion: We provide first evidence that THOR epigenetic modulation drives telomere maintenance in Indian cervical cancer patients. Low menin recruitment to hypermethylated THOR identifies a novel epigenetic axis with dual prognostic and diagnostic potential. The HPV-independent nature of THOR regulation highlights an underexplored therapeutic target for epigenetic therapy in cervical cancer.

Cervical cancer remains the fourth most common malignancy among women worldwide, with limited therapeutic success in advanced and recurrent stages. Conventional treatments, including radiotherapy and chemotherapeutic agents are often limited by off-target toxicity and poor selectivity toward malignant cells. Considering growing interest in phytotherapeutics, the present study evaluates the cytotoxic and genotoxic effects of methanolic extract of Curcuma caesia (MECC) on cervical cancer cells. Human cervical cancer cell lines (HeLa and SiHa) and non-cancerous HEK293T cells were treated with varying concentrations of MECC. Cell viability, proliferation, and oxidative stress were assessed via MTT, cell cycle analysis, and ROS quantification, respectively. DNA damage and repair responses were evaluated using COMET, TUNEL, and γH2A.X foci assays. Senescence was detected by β-galactosidase staining, while apoptotic and DNA damage response proteins were examined through Western blotting. MECC exhibited dose-dependent cytotoxicity in HeLa and SiHa cells while sparing HEK293T cells, indicating selectivity toward malignant cells. Treatment induced cell cycle arrest and significantly reduced intracellular ROS levels. DNA damage was evident from increased comet tail moments, TUNEL positivity, and nuclear accumulation of γH2A.X. MECC further promoted apoptosis, as demonstrated by elevated levels of cleaved caspase-3, Bax, cleaved PARP1, and reduced Bcl-2 expression. Concurrent induction of cellular senescence was also observed. MECC induces apoptosis and senescence, through modulation of oxidative stress and induction of DNA damage in cervical cancer cells. This highlights its potential as a plant-based therapeutic candidate with reduced cytotoxicity toward non-cancerous cells. The online version contains supplementary material available at 10.1186/s12906-026-05351-0.

Background Falcarindiol, a bioactive polyacetylene, has shown cytotoxic effects in several cancers including breast, colorectal, and oral squamous carcinoma, but its pharmacological actions in cervical cancer are not well defined. Objectives This study aims to integrate in silico approaches to define the multi-target pharmacological mechanisms of falcarindiol in cervical cancer, including ADMET profiling, network pharmacology, target prioritization, and molecular docking especially of EGFR/mTOR associated signaling pathways. Simultaneously, the study aims to experimentally verify the anticancer activity of falcarindiol in cervical cancer cells by examining its impacts on cell viability, apoptosis, mitochondrial dysfunction, reactive oxygen species generation, senescence induction, and cell cycle regulation. Methods Pharmacokinetic and toxicity properties were evaluated using in silico ADMET profiling. Potential molecular targets and signaling pathways were identified from integrated databases, with hub genes prioritized by protein–protein interaction analysis. Protein-ligand binding was assessed through docking. Gene expression and prognostic significance were analyzed using public cancer datasets. Functional effects of falcarindiol were validated in HeLa and SiHa cervical cancer cells by MTT assay, Annexin V/PI, and AO/PI staining, mitotracker intensity, H₂DCFDA fluorescence, β-galactosidase staining, and cell cycle analysis. Results Falcarindiol demonstrated favorable ADMET properties and low predicted toxicity. Target prioritization identified EGFR, ERBB2, mTOR, MMP9, and CASP3 as central nodes, with strong interactions confirmed for EGFR and mTOR. Expression analyses revealed upregulation and hypomethylation of these genes in cervical cancer. Falcarindiol reduced viability (IC50 ~ 125–150µM), induced apoptosis, disrupted mitochondrial membrane potential, increased ROS production, and caused G₀/G₁ arrest in vitro. Senescence was also enhanced in treated cells. Conclusion Falcarindiol exerts multi-targeted pharmacological actions in cervical cancer by modulating EGFR/mTOR signaling and apoptotic pathways, supporting its potential as a therapeutic lead compound.

Background Oct4 has critical role in maintaining pluripotency, proliferative potential, and self-renewal capacity in embryonic stem and germ cells. Although Oct4 has been shown to be upregulated in many cancers, its clinical significance in gallbladder carcinoma is poorly understood. Methods We studied the expression profile of Oct4 in 61 GBC and 30 chronic cholecystitis (as control) using real time RT-PCR, western blotting, and immunohistochemistry. The expression data was correlated with clinico-pathological parameters. The diagnostic utility was assessed through ROC curve, and prognostic value was analyzed by Kaplan–Meier method. Results Oct4 was significantly upregulated at mRNA as well as protein levels. The higher mRNA expression shows significant association with late stage, late T stage, and higher grade of tumor. A significant positive correlation was also observed with stage, T stage, and tumor grade. Sum score analysis of protein expression shows positive correlation with stage and the presence or absence of gallstone in tumor samples. The ROC curve analysis revealed the moderate diagnostic potential of Oct4. Kaplan–Meier analysis showed that patients having higher expression of Oct4 were having low mean survival compared with the patients with lower Oct4 expression. Conclusion In conclusion, our data suggests that higher expression of Oct4 may serve as potential biological indicator for tumor aggressiveness and poor prognosis of GBC.

Genes associated with growth factors were previously analyzed in a radiation- and estrogen-induced experimental breast cancer model. Such in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line, MCF-10F, to low doses of high linear energy transfer (LET) α particle radiation (150 keV/μm) and subsequent growth in the presence or absence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation after being irradiated with either a single 60 cGy dose or 60/60 cGy doses of alpha particles. In the present report, the profiling of differentially expressed genes associated with growth factors was analyzed in their relationship with clinical parameters. Thus, the results indicated that Fibroblast growth factor2 gene expression levels were higher in cells transformed by radiation or in the presence of ionizing radiation; whereas the fibroblast growth factor-binding protein 1gene expression was higher in the tumor cell line derived from this model. Such expressions were coincident with higher values in normal than malignant tissues and with estrogen receptor (ER) negative samples for both gene types. The results also showed that transforming growth factor alpha gene expression was higher in the tumor cell line than the tumorigenic A5 and the transformed A3 cell line, whereas the transforming growth factor beta receptor 3 gene expression was higher in A3 and A5 than in Tumor2 cell lines and the untreated controls and the E cell lines. Such gene expression was accompanied by results indicating negative and positive receptors for transforming growth factor alpha and the transforming growth factor beta receptor 3, respectively. Such expressions were low in malignant tissues when compared with benign ones. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expressions were found to be present in all BRCA patients that are BRCA-Basal, BRCA-LumA, and BRCA-LumB, except in BRCA-Her2 patients. The results also indicated that the insulin growth factor receptor gene expression was higher in the tumor cell line Tumor2 than in Alpha3 cells transformed by ionizing radiation only; then, the insulin growth factor receptor was higher in the A5 than E cell line. The insulin growth factor receptor gene expression was higher in breast cancer than in normal tissues in breast cancer patients. Furthermore, Fibroblast growth factor2, the fibroblast growth factor-binding protein 1, transforming growth factor alpha, the transforming growth factor beta receptor 3, and the insulin growth factor receptor gene expression levels were in stages 3 and 4 of breast cancer patients. It can be concluded that, by using gene technology and molecular information, it is possible to improve therapy and reduce the side effects of therapeutic radiation use. Knowing the different genes involved in breast cancer will make possible the improvement of clinical chemotherapy.

Cancer develops in a multi-step process where environmental carcinogenic exposure is a primary etiological component, and where cell–cell communication governs the biological activities of tissues. Identifying the molecular genes that regulate this process is essential to targeting metastatic breast cancer. Ionizing radiation can modify and damage DNA, RNA, and cell membrane components such as lipids and proteins by direct ionization. Comparing differential gene expression can help to determine the effect of radiation and estrogens on cell adhesion. An in vitro experimental breast cancer model was developed by exposure of the immortalized human breast epithelial cell line MCF-10F to low doses of high linear energy transfer α particle radiation and subsequent growth in the presence of 17β-estradiol. The MCF-10F cell line was analyzed in different stages of transformation that showed gradual phenotypic changes including altered morphology, increase in cell proliferation relative to the control, anchorage-independent growth, and invasive capability before becoming tumorigenic in nude mice. This model was used to determine genes associated with cell adhesion and communication such as E-cadherin, the desmocollin 3, the gap junction protein alpha 1, the Integrin alpha 6, the Integrin beta 6, the Keratin 14, Keratin 16, Keratin 17, Keratin 6B, and the laminin beta 3. Results indicated that most genes had greater expression in the tumorigenic cell line Tumor2 derived from the athymic animal than the Alpha3, a non-tumorigenic cell line exposed only to radiation, indicating that altered expression levels of adhesion molecules depended on estrogen. There is a significant need for experimental model systems that facilitate the study of cell plasticity to assess the importance of estrogens in modulating the biology of cancer cells.