PROBIOTIC METABOLITES OF OLIGOMERIC PROANTHOCYANIDIN REDUCE NICOTINE-DERIVED NITROSAMINE KETONE ACETATE-INDUCED DNA DAMAGE IN HUMAN LUNG EPITHELIAL AND FETAL HEPATIC CELLS IN VITRO

Abstract

Potential of proanthocyanidin (PAC) in cancer risk reduction is dependant on the biotransformation process by colonic microbiotia. Seven selected microbial metabolites of proanthocyanidins (MMP) were evaluated for their ability to reduce 4-[(acetoxymethyl) nitrosamino]-1-(3-pyridyl)-1-butanone (NNKOAc)-induced DNA damage in human lung epithelial (BEAS-2B) and fetal hepatic (WRL-68) cells. Pyrogallol (PG) in BEAS-2B cells and pyrocatechol (PC) in WRL-68 cells reduced the DNA damage as measured by the γ-H2A.X assay. Western blot analysis suggested that PG- and PC-mediated DNA damage reduction is driven by alterations in the DNA damage response (DDR) pathways. Oligomeric apple peel (AP)-PAC and commercial grape seed (GS)-PAC were biotransformed by Lactobacillus rhamnosus and Lactobacillus casei. Phenolic metabolites identified after biotransformation of GS-PAC by L. rhamnosus were PG, PC, 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, p-coumaric acid, methyl hippuric acids, 4-hydroxyphenylvaleric acid, and sinapic acid. To confirm the PAC-mediated chemoprevention, an experimental animal model of NNKOAc-induced A/J mice can be recommended.