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.
Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest