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Anticancer Agents Med Chem. 2019 Sep 30. doi: 10.2174/1871520619666190930123520. [Epub ahead of print]

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

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Medical Biochemistry Department, Medical Division, National Research Centre, Dokki, 12622, Cairo. Egypt.
Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki 12622, Cairo. Egypt.
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo. Egypt.



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.


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.


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 enhancing apoptosis through 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.


Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.


apoptosis; cell cycle arrest; cisplatin; hepatocellular carcinoma; synergistic effect; α-solanine

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