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Chrysin Modulates Metastasis Associated and Tumor Suppressor Gene Expression in HeLa Cells: Implications for Cervical Cancer Molecular Pathways | ||
| Journal of Epigenetics | ||
| مقالات آماده انتشار، پذیرفته شده، انتشار آنلاین از تاریخ 11 مهر 1405 | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22111/jep.2026.55613.1109 | ||
| نویسندگان | ||
| Seyyedeh Zahra Mousavi Benehour؛ Hadi Habibollahi* ؛ Leila Asadpour | ||
| Department of Biology, Ra.C., Islamic Azad University, Rasht, Iran. | ||
| چکیده | ||
| Background: Cervical cancer progression is driven by dysregulated proliferation, impaired apoptosis, and altered expression of metastasis-related and tumor-suppressor genes. Chrysin, a bioactive flavonoid, has shown anticancer activity across multiple malignancies; however, its molecular and cellular effects in cervical cancer remain incompletely characterized. This study investigated the antiproliferative, pro-apoptotic, and gene-modulatory effects of chrysin in HeLa cells. Methods: HeLa cells were treated with chrysin for 48 hours. Cell viability was assessed by MTT assay, and IC₅₀ was determined by nonlinear regression. Apoptosis was quantified by Annexin V-FITC/PI flow cytometry. Expression levels of MMP3, NRP2, and APC were evaluated by quantitative real-time PCR. Statistical analyses were performed using ANOVA with appropriate post hoc testing. Results: Chrysin significantly inhibited HeLa cell viability in a concentration-dependent manner, with an IC₅₀ of 108.0 µg/ml. Flow cytometric analysis revealed a marked shift from viability to apoptosis. In the control group, viable cells constituted 69.7%, early apoptosis 6.5%, late apoptosis 4.89%, and necrosis 6.89%. Following chrysin exposure, viability decreased to 59.0%, while early apoptosis increased to 8.93% and late apoptosis rose substantially to 28.9%, indicating dominant activation of apoptotic pathways; necrosis remained limited at 3.17%. Gene expression analysis showed significant downregulation of MMP3 (0.4-fold; P < 0.01) and NRP2 (0.75-fold; P < 0.05), alongside upregulation of the tumor suppressor APC (1.6-fold; P < 0.01). Conclusions: Chrysin exerts potent anticancer activity in HeLa cells by reducing viability, enhancing apoptosis, and inducing coordinated transcriptional modulation of metastasis-associated and tumor-suppressive genes. These integrated effects highlight chrysin as a promising natural candidate for further mechanistic and preclinical exploration in cervical cancer therapy. | ||
| کلیدواژهها | ||
| Chrysin؛ Cervical cancer؛ Apoptosis؛ Gene expression regulation؛ HeLa cells | ||
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