Elucidating the anticancerous efficacy of genistein via modulating HPV (E7 and E6) oncogenes expression and apoptotic induction in cervical cancer cells
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Published on: September 18, 2013
Pratibha Pandey1,2, Seema Ramniwas3, Shivam Pandey4
1Centre for Research Impact & Outcome, Chitkara University Institute of Engineering & Technology, Chitkara University, Rajpura, Punjab, India.
Abstract:
In recent years, genistein has garnered increased interest for its ability to inhibit numerous deregulated targets associated with cancer progression and induction of programmed cell death and antiproliferative activities in human carcinoma cells. Cancer etiology is influenced via multiple disrupted signaling pathways. This study therefore directed toward investigating genistein efficacy in modulating mRNA expression levels of two crucial Human Pappiloma Virus (HPV) (E7 and E6) oncogenes for cancer treatment. Moreover, the inhibitory effects of genistein for HPV (E7 and E6) oncogenes in cervical carcinoma have not yet been reported. Current study investigated inhibitory potential of genistein in HPV (E7 and E6) oncogenes in HeLa cells. These oncogenes are known to deactivate many tumor suppressor proteins (p53 and pRB). Genistein therapy resulted in decreased cell proliferation and increased cell accumulation in the G (G0/G1) phase in HeLa cell lines. In addition, genistein therapy has resulted in the suppression of HPV (E7 and E6) gene expression and simultaneously increasing expression levels of p53 and pRB mRNA levels. As a consequence, there has been an activation of a series of caspases (3, 8, and 9), resulting in their cleavage. Consequently, our data suggests that genistein could be a powerful candidate for treating cervical cancer by targeting two important oncogenes involved in viral development. However, more in vitro research on primary cervical cancer cells is required to validate the clinically relevant efficacy of genistein against cervical cancer.
Insights
Genistein effectively suppressed Human Papillomavirus (HPV) oncogenes E7 and E6 in cervical cancer cells. This led to increased tumor suppressor proteins and induced cancer cell death, suggesting potential for cervical cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Genistein exhibits anti-cancer properties by inhibiting cancer progression and inducing apoptosis.
- Human Papillomavirus (HPV) oncoproteins E7 and E6 are crucial in cervical cancer development, deactivating tumor suppressors p53 and pRB.
- The inhibitory effect of genistein on HPV E7 and E6 oncogenes in cervical carcinoma remains largely unexplored.
Purpose of the Study:
- To investigate genistein's efficacy in modulating mRNA expression of HPV E7 and E6 oncogenes in cervical carcinoma.
- To evaluate genistein's impact on cell proliferation and cell cycle progression in HeLa cells.
- To determine genistein's effect on the expression of p53 and pRB tumor suppressor proteins and caspase activation.
Main Methods:
- HeLa cells were treated with genistein.
- mRNA expression levels of HPV E7, E6, p53, and pRB were analyzed.
- Cell proliferation and cell cycle distribution were assessed.
- Caspase activation (caspases 3, 8, and 9) was evaluated.
Main Results:
- Genistein treatment reduced cell proliferation and increased G0/G1 phase cell accumulation in HeLa cells.
- Genistein suppressed HPV E7 and E6 gene expression.
- Genistein increased the expression of p53 and pRB mRNA.
- Genistein treatment activated caspases 3, 8, and 9, leading to their cleavage.
Conclusions:
- Genistein demonstrates significant inhibitory potential against HPV E7 and E6 oncogenes in cervical cancer cells.
- Genistein promotes apoptosis by upregulating tumor suppressor proteins and activating caspases.
- Genistein represents a promising therapeutic candidate for cervical cancer, warranting further in vitro investigation with primary cells.
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