Induction of UDP-glucuronosyltransferase 1A by naturally occurring phytochemicals in human hepatoma cells
Keywords:tannic acid, protocatechuic acid, indole-3-carbinol, phenethyl isothiocyanate, UGT1A, HepG2
AbstractUDP-glucuronosyltransferases (UGTs) are important detoxification and drug-metabolizing enzymes, which catalyse the glucuronidation of exogenous and endogenous chemicals. The anti-carcinogenic activity of dietary phytochemicals is partly attributed to the induction of phase II enzymes, including UGT1A. Our earlier study showed that protocatechuic acid increased UGT activity in rat liver. A similar effect was observed for indole-3-carbinol and phenethyl isothiocyanate in rat liver. In this study we assessed the effect of protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate on the expression and protein level of UGT1A in hepatocellular carcinoma HepG2 cells. Cells were incubated with 2µM and 10µM of protocatechuic acid, tannic acid, or indole-3-carbinol and 1µM and 5µM of phenethyl isothiocyanate for 72 hours. Transcript level was measured by RT-PCR and protein level by the immunoblot assay. Treatment with protocatechuic acid, tannic acid, indole-3-carbinol and phenethyl isothiocyanate induced the expression and protein level of UGT1A. Phenethyl isothiocyanate increased the mRNA of UGT1A to the most extent (0.28–5.7 fold change, p < 0.05). Increased expression of UGT1A was accompanied by the enhancement of its protein level, with the exception of protocatechuic acid at the dose of 2µM. Overall, isothiocyanates and indoles were more potent as UGT inducers than phenolic acids. Collectively, the results suggest that the induction of UGT1A could contribute to the hepatoprotective and chemopreventive properties of these phytochemicals.
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