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.
Ionizing radiation but not anticancer drugs causes cell cycle arrest and failure to activate the mitochondrial death pathway in MCF-7 breast carcinoma cells
