Modulation of NRF2 and UGT1A expression by epigallocatechin-3-gallate in colon cancer cells and BALB/c mice

Zhi-mian Zhang, Xiao-yun Yang, Jun-hua Yuan, Zi-yuan Sun, Yan-qing Li
Chinese Medical Journal 2009 July 20, 122 (14): 1660-5

BACKGROUND: Green tea is an important source of flavonoids in human diets and epidemiological data correlate green tea consumption with a reduced cancer risk. Given its complicated properties at effective concentrations, we put epigallocatechin-3-gallate (EGCG) that previously reported on its anti-proliferative activities against several cancer cell lines on our research agenda to further examine the mechanism of its chemopreventive potential.

METHODS: RNA interference (RNAi) expression vector pSilencer 3.1-H1 was used to construct recombinant nuclear factor erythroid 2 related factor 2 (Nrf2)-targeting RNAi plasmids. EGCG (5 microg/ml) was added into the culture fluid of cells before and after transfection. RT-PCR and Western blotting were used to detect the expression of uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A in cells. Forty male BALB/c mice were assigned to four groups: a normal unexposed control and three groups treated with varying doses of EGCG. Four weeks later, the mice were sacrificed, and their colon tissues were subjected to mRNA and protein expression of Nrf2 and UGT1A via RT-PCR and Western blotting analysis.

RESULTS: EGCG up-regulated the expression of Nrf2 and increased the level of UGT1A in cells. The blockade of Nrf2 activity via RNA intervention largely attenuated the induction of UGT1A expression by EGCG. In mice, the mRNA and protein levels of Nrf2 and UGT1A detected by RT-PCR and Western blotting increased (both P < 0.05 compared with the control). This increase in Nrf2 expression also had a positive correlation with an increased UGT1A expression.

CONCLUSIONS: EGCG mediated its effect in part by inducing the NRF2 signaling pathway and increasing UGT1A expression. Both in vitro and in vivo studies demonstrated the role of NRF2 and UGT1A expression in the potential use of EGCG as a possible chemopreventive agent and supported further study of EGCG for cancer treatment.

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