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Anti-Cancer Agents in Medicinal Chemistry

Author(s): Sherien M. El-Daly*, Shaimaa A. Gouhar, Amira M. Gamal-Eldeen, Fatma F. Abdel Hamid, Magdi N. Ashour and Nahla S. Hassan

DOI: 10.2174/1871520619666190930123520

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Synergistic Effect of α-Solanine and Cisplatin Induces Apoptosis and Enhances Cell Cycle Arrest in Human Hepatocellular Carcinoma Cells

Page: [2197 - 2210] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

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.

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 carcinoma.

Keywords: α-solanine, cisplatin, hepatocellular carcinoma, apoptosis, cell cycle arrest, synergistic effect.

Graphical Abstract

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