Lactobacillus rhamnosus GG Inhibits BID Dependent-Apoptosis in Human Hepatocellular Carcinoma Cells Exposed to Patulin

Abstract

Patulin, a mycotoxin, which is a major contaminant in apple juices, has contributed immensely to the occurrence of liver diseases. Consumption of apple juice could over long period of time become harmful to the health of individuals with pre-existing liver disease. Probiotics are known for their role in patulin removal from aqueous media. In this study, we investigated the effects of a probiotic microorganism on patulin toxicity in hepatocellular carcinoma (HepG2) cells and established the protective effect of Lactobacillus rhamnosus (LGG) as mediated by induction of BH3-interacting domain antagonist (BID) in response to patulin toxicity. After 24 hours of patulin exposure followed by 24 hours of treatment with Lactobacillus rhamnosus, cells proliferation decreased with increasing patulin exposure in samples without LGG pre-treatment, whereas with increasing concentration of patulin, cells were relatively rescued in LGG treated samples. It was further observed that pre-treatment of LGG with polysaccharide gums led to a decline in cell proliferation with increasing patulin exposure. Compare to the control, the expression of p53 upregulated moderator of apoptosis (PUMA) increased slightly by 7 % at 10µM patulin exposure in treatment and decreased by 30% in untreated cell. However, the expression of BID decreased by 26% in treatment compared to the control. We further established that the protective effect of Lactobacillus rhamnosus was mediated by the inhibition of BID. Our findings suggest that Lactobacillus rhamnosus GG could potentially function as a therapeutic agent to reverse the damaging effect of patulin on the liver of individuals with pre-existing liver disease.

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“…LGG is a widely used probiotic strain that has been evaluated for the treatment of diarrhea ( 138 ), antiproliferative effects on the cells of colon adenocarcinoma ( 139 ), suppressive effects on inflammation during Helicobacter infection in gastric adenocarcinoma cells ( 140 ), and high-fructose diet-induced NAFLD ( 141 ). In the present review, we found that probiotic LGG can decrease the risk of HCC through multiple pathways, including DNA damage ( 55 ), inflammatory and cell differentiation ( 56 ), and human hepatoma cell apoptotic regulation ( 58 ). Probiotics interact with the host and the microbiome via molecular effectors as metabolic products through the gastrointestinal microenvironment and mediate health benefits ( 142 ).…”

“…There have been several in vitro investigations of the effects of This study reported the beneficial role of probiotics in the inhibition of liver fibrogenesis and the prevention of liver cancer. Another study has shown the protective effects of LGG against patulin-induced apoptosis in HepG2 cells by regulating the levels of proapoptotic BCL2 proteins p53 upregulated modulator of apoptosis and BH3-interacting domain death agonist in vitro (58).…”