Oroxylin A exerts antiproliferative effects through downregulation of E6 and E7 oncogenes in cervical cancer HeLa cells
Numerous plant compounds have shown promising antitumor potential against cervical cancer. Plant-based compounds offer abundantly available, easy, and inexpensive methods of treatment over genome-editing technologies (immunotherapeutics). Many flavonoids directly abrogated HPV-E6/E7 activity with a concomitant apoptotic conclusion. Cervical cancer initiation and progression are entirely dependent on the oncogenes E6 and E7 (constitutively expressed) leading to tumorigenesis. Therefore, the manipulation of these oncogenes is the most prominent form of cervical cancer therapeutics. To further explore the mechanism underlying apoptosis induction, ROS generation, apoptosis-related gene expression (Bcl-2, caspases-3, caspases-8, and caspases-9), viral oncogenes (E6/E7), and tumor suppressor proteins (p53/pRb) were evaluated using MTT, cell cycle arrest, Hoechst, docking, and RT-PCR analysis. This study showed that oroxylin A (OrA) effectively inhibited HeLa cell proliferation at the respective doses. This study suggests that OrA inhibits E6/E7 mRNAs, leading to the upregulation of p53/pRb (tumor suppressor genes) in HeLa cells. Moreover, OrA induced p53-mediated apoptosis induction, activating the transcription of various proapoptotic genes, including Bcl-2 and Bax. Alternatively, p53 triggers apoptosis by promoting the caspase activation. In conclusion, OrA targeting E6/E7 was highly effective in inhibiting cancer cell proliferation via the upregulation of suppressor genes in cervical cancer.