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Oroxylin A exerts antiproliferative effects through downregulation of E6 and E7 oncogenes in cervical cancer HeLa
Shan Hu1, Yongting Lu2, Pratibha Pandey3
1Department of Anesthesiology, The Taiyun Hospital of Peking University First Hospital/Taiyuan Central Hospital of Shanxi Medical University, Taiyuan, 030000, China.
Abstract:
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.
Insights
Oroxylin A (OrA), a plant compound, effectively inhibits cervical cancer cell growth by targeting human papillomavirus (HPV) E6/E7 oncogenes. This leads to tumor suppressor gene activation and apoptosis, offering a promising natural therapeutic approach.
Area of Science:
- Phytochemistry
- Oncology
- Molecular Biology
Background:
- Cervical cancer progression is driven by HPV E6 and E7 oncogenes.
- Plant-derived compounds, particularly flavonoids, show potential as natural anticancer agents.
- Targeting HPV oncogenes is a key therapeutic strategy for cervical cancer.
Purpose of the Study:
- To investigate the anti-cervical cancer effects of oroxylin A (OrA).
- To elucidate the molecular mechanisms of OrA action, including its impact on HPV E6/E7, apoptosis, and tumor suppressor genes.
Main Methods:
- MTT assay for cell proliferation
- Cell cycle arrest analysis
- Hoechst staining for apoptosis
- Molecular docking studies
- RT-PCR for gene expression analysis (E6/E7, p53, pRb, Bcl-2, Bax, caspases)
Main Results:
- Oroxylin A significantly inhibited HeLa cell proliferation in a dose-dependent manner.
- OrA downregulated HPV E6/E7 oncogene expression.
- OrA upregulated tumor suppressor proteins p53 and pRb.
- OrA induced apoptosis through p53-mediated pathways, activating proapoptotic genes and caspases.
Conclusions:
- Oroxylin A demonstrates significant anticancer activity against cervical cancer by targeting HPV E6/E7 oncogenes.
- OrA promotes apoptosis and inhibits proliferation via the p53/pRb tumor suppressor pathway.
- OrA represents a promising natural compound for cervical cancer therapy.
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