Biotransformation of Cranberry Proanthocyanidins to Probiotic Metabolites byLactobacillus rhamnosusEnhances Their Anticancer Activity in HepG2 CellsIn Vitro

Abstract

This study was designed to unravel the role ofLactobacillus rhamnosusin the bioconversion of cranberry proanthocyanidins and cytotoxicity of resulting metabolites to hepatocellular carcinoma HepG2 cells. Crude (CR) and flavonol+dihydrochalcone- (FL+DHC-), anthocyanin- (AN-), proanthocyanidin- (PR-), and phenolic acid+catechin- (PA+C-) rich fractions were subjected to fermentation withL. rhamnosusat 37°C for 12, 24, and 48 h under anaerobic conditions. The major metabolites produced by bioconversion of polyphenols were 4-hydroxyphenylacetic acid, 3-(4-hydroxyphenyl)propionic acid, hydrocinnamic acid, catechol, and pyrogallol. Furthermore, cytotoxicity of the biotransformed extracts was compared to their parent extracts using human hepatocellular carcinoma HepG2 cells. The results showed that PR-biotransformed extract completely inhibited HepG2 cell proliferation in a dose- and time-dependent manner with IC50values of 47.8 and 20.1μg/mL at 24 and 48 h, respectively. An insight into the molecular mechanisms involved revealed that the cytotoxic effects of PR at 24 h incubation were mitochondria-controlled and not by proapoptotic caspase-3/7 dependent. The present findings suggest that the application of a bioconversion process using probiotic bacteria can enhance the pharmacological activities of cranberry proanthocyanidins by generating additional biologically active metabolites.