Cytotoxic activity of Solanum tuberosum polyphenolic extracts in human hepatocarcinoma cells is mediated by apoptosis and autophagy

Abstract

Hepatocellular carcinoma (HCC) is one of the most frequent tumors worldwide, associated with a high mortality rate. HCC patient´s prognosis remains unfavorable, mainly due to late diagnosis and treatment instauration delay. Thus, there is an urgent requirement for the development of new therapeutical options, particularly for advanced HCC patients. Polyphenols are specialized plant metabolites, which have been broadly characterized for their beneficial effects on human health. Potato is one of the main sources of these compounds in human diet, due to its high consumption. The objectives of this study were to: characterize the polyphenolic composition, analyze the antioxidant properties, evaluate the cytotoxic activity in human tumoral hepatocytes, and describe the molecular mechanisms involved in cell death, of potato polyphenolic extracts (PPEs) from the pigmented Andigena cultivar CL658. The results showed that phenolic acids were the main group of polyphenols in the extracts, chlorogenic acid being the major compound, followed by caffeic acid. HPLC-DAD profile showed pelargonidin as the principal anthocyanin. The treatment of HCC cell lines with the cytotoxic concentration 50 (CC50 ) of the PPEs resulted in cytotoxicity, evidenced by increases in the percentage of dead cells (5-10%) after treatments. This cytotoxic effect was mainly due to apoptosis activation, evidenced by modulation of the Bcl-2 family proteins expression, in favor of pro-apoptotic members over anti-apoptotic in the final balance. PPEs also induced autophagy, indicated by increased LC3 expression (122-274%) and autophagosomes, and reduced p62 expression (32-48%), in variable magnitudes according to the treated cell line. Overall, these results support the potential use of PPEs from the cultivar CL658 as a source of bioactive compounds for novel treatments against HCC.