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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.

Author information

1
Medical Biochemistry Department, Medical 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.
3
Biochemistry Department, Faculty of Science, Ain Shams University, Cairo. Egypt.

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 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.

CONCLUSION:

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.

KEYWORDS:

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

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