Journal
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
Volume 19, Issue 18, Pages 2197-2210Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1871520619666190930123520
Keywords
alpha-solanine; cisplatin; hepatocellular carcinoma; apoptosis; cell cycle arrest; synergistic effect
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Funding
- National Research Centre, Cairo, Egypt [11010332]
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Aim: The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid alpha-solanine on human hepatocellular carcinoma cells was evaluated. Methods: HepG2 cells were exposed to low doses of alpha-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement. Results: alpha-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G(2)/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression. Conclusion: Our study provides strong evidence that a combination treatment of low doses of alpha-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.
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