Amentoflavone, a biflavonoid with potential anticancer properties against viral oncoprotein E6 in Human papilloma virus-16 (HPV-16) positive cervical cancer cells.

Abstract

Cervical cancer is predominantly associated with Human Papillomavirus (HPV) infection via HPV16-E6This interdisciplinary investigation investigates the effects of amentoflavone, a bioflavonoid on HPV16-E6, unravelling its impact on the protein's structural dynamics to explore its potential as a therapeutic agent for cervical cancer. MD simulations demonstrated stable binding dynamics between amentoflavone and HPV16-E6. RMSD analysis revealed alterations in the E6 protein structure, and Gibbs binding free energy calculations indicated an energetically favourable interaction. Control simulations enhanced the interpretability of the results. Amentoflavone inhibited the proliferation of SiHa and CaSki cells with GI₅₀ values of 47.2 ± 9.64 μM and 29.1 ± 4.38 μM respectively. Treatment with amentoflavone promoted early and late-phase apoptosis in these cells. The compound reduced HPV-16 E6 while increasing p53-positive populations in SiHa and CaSki cells. In conclusion, the findings of this study suggest that amentoflavone may act as a potential inhibitor of HPV16-E6, disrupting its structural integrity and dynamics.