Abstract
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.
Highlights
Human papillomavirus (HPV)-induced cervical cancer has been recognized as one of the major health issues among women and accounts for high mortality rate due to its poor prognosis and late diagnosis [1,2]
HPV18+ human cervical cancer HeLa cell lines were obtained from National Centre for Cell Science (NCCS), Pune, India
In order to further explore the correlation of reactive oxygen species (ROS) generation with apoptosis in rutin-treated HeLa cancer cells, we investigated the effect of rutin on HeLa cells in presence of 10 mM NAC by employing MTT assay
Summary
Human papillomavirus (HPV)-induced cervical cancer has been recognized as one of the major health issues among women and accounts for high mortality rate due to its poor prognosis and late diagnosis [1,2]. Both initial establishment and final progression of this cancer have been fully associated with the constitutive expression of two major oncogenes including E6 and E7. E6 and E7 are recognized as key oncoplayers driving whole HPV-mediated cervical carcinogenesis by the establishment of six potential hallmarks of cancer [6]. Earlier literatures have proven that cancerous cells undergo apoptosis (senesce) in the absence of License 4.0 (CC BY)
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