Enhancing the therapeutic chemosensitivity of hepatocellular carcinoma cells using alpha-solanine

Abstract

Hepatocellular carcinoma (HCC) is one of the world's most common malignancies, accounting for 8.2% of all cancer occurrences and the world's second most common cause of cancer-related deaths. Chemotherapy is one of the most important treatment modalities for advanced HCC. Cisplatin is a platinum based drug that exerts its cytotoxicity through interacting with cellular DNA and ultimately triggers apoptotic cell death however, the clinical application of cisplatin is limited by severe side effects ad toxicity associated with the high clinically applied doses. α-Solanine is a steroid alkaloid with an anti-tumor effect on several cancer types and its cytotoxic effect was mediated by induction of apoptosis. The present study aimed at assessing the anti-tumor effect of the natural compound α-solanine in combination with low concentration of cisplatin on human hepatocellular carcinoma cell line HepG2. Human hepatocellular carcinoma cell line HepG2 were cultured and treated with different doses of cisplatin or α-solanine individually or in combination. Initially we evaluated the cytotoxic effect of α-solanine and cisplatin on cell viability using MTT assay. The effect of all treatment modalities on cell cycle arrest was assessed using flow cytometer. Apoptosis was detected in HepG2 cells using the Apoptosis Detection Kit Annexin V-FITC. The activation of the apoptotic process following treatment of HepG2 cells was evaluated using Caspase-Glo® 3/7 luminescent assay. Total RNA including miRNA was extracted and purified from HepG2 cells for the estimation of changes in survivin, Bcl-2 and miR-21 expression after different treatments. CD133 representing cells were estimated by flow cytometer.