Chrysin Treatment is Associated with Altered Microrna Expression and Reduced Levels of HPV16 E6 Protein in Caski Cervical Cancer Cells

Persistent infection with high-risk human papillomavirus type 16 (HPV16) is a major cause of cervical cancer and is associated with viral oncoproteins that disrupt tumor suppressor pathways and influence cellular microRNA (miRNA) expression. Given increasing interest in phytochemicals as potential anticancer agents, this study evaluated the effects of chrysin, a natural flavonoid, on cell viability, selected cancer-related miRNAs, and HPV16 E6 protein levels in HPV16-positive CaSki cervical cancer cells. CaSki cells and normal human dermal fibroblasts (HDF) were treated with chrysin (31.5–500 µg/ml) for 24 and 48 h. Cell viability was assessed by MTT assay. Expression of miR-34a, miR-218, miR-20a, miR-195, and miR-23b was quantified by qRT-PCR (2−ΔΔCt method), and E6 protein levels were analyzed by Western blot. Chrysin selectively reduced CaSki cell viability with minimal toxicity toward HDF cells, resulting in a high selectivity index. Treatment was associated with increased expression of miR-34a (10.05-fold, P < 0.0001) and miR-218 (5.64-fold, P < 0.01), a moderate increase in miR-20a (1.7-fold, P < 0.05), decreased miR-195 expression (0.18-fold, P < 0.01), and no significant change in miR-23b. A significant reduction in E6 protein levels was also observed (0.64 ± 0.01 vs. control, P < 0.001). These findings indicate that chrysin treatment is associated with selective cytotoxicity and concurrent modulation of HPV16 E6 protein levels and several cancer-related miRNAs in CaSki cells. Further studies in additional cellular models and mechanistic systems are required to clarify the underlying pathways.