4.6 Article

Elucidation of rutin's role in inducing caspase-dependent apoptosis via HPV-E6 and E7 down-regulation in cervical cancer HeLa cells

Journal

BIOSCIENCE REPORTS
Volume 41, Issue 6, Pages -

Publisher

PORTLAND PRESS LTD
DOI: 10.1042/BSR20210670

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Funding

  1. Noida Institute of Engineering and Technology (NIET), Greater Noida

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Recent research has found that rutin exhibits inhibitory potential against several oncotargets in human cancer cells, particularly demonstrating effects on E6 and E7 oncoproteins in cervical cancer. By modulating cell cycle progression and altering protein expression levels, rutin induces apoptosis in HeLa cells and shows significant anti-tumor effects in both in vitro and in vivo experiments. Additionally, in silico studies support the findings by showing strong binding energy against selected target oncoproteins, suggesting rutin as a potential drug candidate for cervical cancer management.
Over the recent few years rutin has gained wider attention in exhibiting inhibitory potential against several oncotargets for inducing apoptotic and antiproliferative activity in several human cancer cells. Several deregulated signaling pathways are implicated in cancer pathogenesis. Therefore we have inclined our research towards exploring the anticancerous efficacy of a very potent phytocompound for modulating the incontinent expression of these two crucial E6 and E7 oncogenes. Further, inhibitory efficacy of rutin against human papillomavirus (HPV)-E6 and E7 oncoproteins in cervical cancer has not been elucidated yet. This research addresses the growth inhibitory efficacy of rutin against E6 and E7 oncoproteins in HeLa cells, which is known to inactivate several tumor suppressor proteins such as p53 and pRB. Rutin treatment exhibited reduced cell viability with increased cell accumulation in G0/G1 phase of cell cycle in HeLa cell lines. Additionally, rutin treatment has also led to down-regulation of E6 and E7 expression associated with an increased expression of p53 and pRB levels. This has further resulted in enhanced Bax expression and decreased Bcl-2 expression releasing cytochrome c into cytosol followed by caspase cascade activation with cleavage of caspase-3, caspase-8 and caspase-9. Further, in silico studies have also supported our in vitro findings by exhibiting significant binding energy against selected target oncoproteins. Therefore, our research findings might recommend rutin as one of the potent drug candidate in cervical cancer management via targeting two crucial oncoproteins associated with viral progression.

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