Document Type : Essay Abstract
Authors
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Medical Biochemistry Department, Medical Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt
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Department, Faculty of Science, Ain Shams University, Cairo, Egypt
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Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
4
1-Medical Biochemistry Department, Medical Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt 2-Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki 12622, Cairo, Egypt;
Abstract
Thesis Abstract
Background: Anti-cancer chemotherapy although effective it inducesserious adverse effects. In addition, cancer cells can develope resistance to chemotherapy. 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 α-solanine on human hepatocellular carcinoma cells was evaluated. Materials and Methods: HepG2 cells were exposed to low doses of α-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: α-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 G2/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 α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular arcinoma.
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