Cytotoxicity of bioactive polymeric fractions from grape cell culture on human hepatocellular carcinoma, murine leukemia and non-cancerous PK15 kidney cells.
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 microM), the cytotoxicity of subfractions on HepG2 cells was TP-6-5 (maximal toxicity=71.8%; ED(50) = 14.1 microM), TP-6-6 (maximal toxicity=64.3%; ED(50) = 67.0 microM), and TP-6-4 (maximal toxicity = 27.6%; ED(50) = 118.0 microM) 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.
Jo
Jeong-Youn
JY
Department of Natural Resources and Environmental Sciences, 1021 Plant Sciences Laboratory MC 634, University of Illinois at Urbana-Champaign, 1201 S. Dorner Drive, 61801, USA.
de Mejia
Elvira Gonzalez
EG
Lila
Mary Ann
MA
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007939:Leukemia L1210 / Q000188:drug therapy*; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology; D027843:Vitis / Q000737:chemistry / Q000166:cytology
D005419:Flavonoids; D010936:Plant Extracts