Cytotoxicity of bioactive polymeric fractions from grape cell culture on human hepatocellular carcinoma, murine leukemia and non-cancerous PK15 kidney cells

Abstract

Previously, we isolated two fractions (TP-4 and TP-6) from grape cell culture that were potent catalytic inhibitors in a human DNA topoisomerase II assay for cancer chemoprevention. The objectives of this study were to further assess cytotoxicity of these fractions on cancerous and non-cancerous cells, and to subfractionate and characterize the composition of TP-6, a fraction that was selectively cytotoxic to carcinoma cell lines. Both TP-4 and TP-6 provided significant cytotoxicity to L1210 mouse leukemia cells. Only TP-6, a procyanidin-rich fraction, significantly reduced viability in HepG2 human liver cancer cells, yet unlike resveratrol, caused no cytotoxicity to non-cancerous PK15 pig kidney cells. After further subfractionation of TP-6 (maximal toxicity = 67.2%; ED 50 = 50.5 μM), the cytotoxicity of subfractions on HepG2 cells was TP-6-5 (maximal toxicity = 71.8%; ED 50 = 14.1 μM), TP-6-6 (maximal toxicity = 64.3%; ED 50 = 67.0 μM), and TP-6-4 (maximal toxicity = 27.6%; ED 50 = 118.0 μM) in descending order. LC–ESI/MS data suggested that cytotoxicity of these procyanidin mixtures to HepG2 cells was proportional to the degree of polymerization. Because TP-6 and its subfractions were selectively cytotoxic to cancerous cell lines tested, they warrant further investigation as potential natural anticancer agents.