RT Journal Article
SR Electronic
T1 Cytoprotective Effect of 20(S)-Rg3 on Benzo(α)pyrene-induced DNA Damage
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP dmd.111.039503
DO 10.1124/dmd.111.039503
A1 Po Ying Poon
A1 Hoi Hin Kwok
A1 Patrick Y.K. Yue
A1 Mildred S.M. Yang
A1 Nai Ki Mak
A1 Chris K.C. Wong
A1 Ricky N.S. Wong
YR 2011
UL http://dmd.aspetjournals.org/content/early/2011/09/28/dmd.111.039503.abstract
AB Benzo(α)pyrene (BaP) is a polycyclic aromatic hydrocarbon ubiquitously existed in the environment. Its metabolites have been shown to cause DNA damage and cellular dysfunction in human. Panax ginseng C.A. Meyer is a Chinese medicinal herb, and ginsenosides are the main active constituent of ginseng. Accumulating evidences indicated that ginseng extract and ginsenosides possess cytoprotective effects. In this study, the protective effect of ginsenosides on BaP-induced DNA damage in human dermal fibroblasts (HDFs) and HepG2 cells was investigated. The genotoxic effect of BaP was measured by comet assay. Results showed that the tail moment was increased in BaP-treated cells, but co-treatment of ginsenoside 20(S)-Rg3 can significantly decrease BaP-induced DNA damage. Downstream mechanistic study revealed that 20(S)-Rg3 increased the gene expression of an important phase II detoxifying enzyme NAD(P)H: quinine oxidoreductase 1 (NQO1). The effect was also associated with the activation of protein kinase B (PKB/Akt) and nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). These results indicated that 20(S)-Rg3 might protect HDFs from BaP-induced DNA damage through the activation of PI3K/Akt/Nrf2 pathway. Our results also demonstrated that 20(S)-Rg3 is a functional ligand of pregnane X receptor (PXR), a nuclear receptor which mediates the induction of drug clearance pathways. Subsequent knockdown of PXR expression by small interfering RNA confirmed the involvement of PXR on the protective effects of 20(S)-Rg3 against BaP-induced DNA damage. In summary, ginsenoside 20(S)-Rg3 can protect BaP-induced genotoxicity in human cells, suggesting that ginseng may serve as a natural cytoprotective agent against environmental carcinogens.