Trans-resveratrol-mediated inhibition of beta-oestradiol conjugation in MCF-7 cells stably expressing human sulfotransferases SULT1A1 or SULT1E1, and human liver microsomes.
High concentrations of endogenous oestradiol (E2) correlate with the proliferation of cancer cells. Resveratrol (a dietary chemopreventive agent) at high concentrations has an anti-oestrogenic effect. E2 and resveratrol are conjugated via common uridine diphosphoglucuronosyltransferase (UGT) and sulfotransferases (SULT) enzymes. Experiments were conducted in MCF-7 mammalian cells stably expressing human SULT1A1 or SULT1E1 to observe the effect of resveratrol on E2-mediated cell proliferation. The combination of E2 and resveratrol did have a proliferative effect in cells expressing SULT1E1, but not in those expressing SULT1A1. The effect of resveratrol (1-500 microM) on the glucuronidation of E2 (0.25-2.25 microM) was characterized in human liver microsomes. The highest resveratrol concentration significantly decreased the intrinsic clearance of E2 glucuronidation. The results corroborate the reported significant inhibition of SULT1E1-mediated E2 sulfation in vitro by resveratrol. Thus, resveratrol may interact with E2 in vivo by inhibiting its conjugation.
Ung
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D
Pharmaceutical Sciences, Temple University, Philadelphia, PA 19140, USA.
Nagar
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S
D015239:Arylsulfotransferase / Q000096:biosynthesis*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D015238:Sulfotransferases / Q000096:biosynthesis*
D004965:Estrogen Antagonists; D013267:Stilbenes; D004958:Estradiol; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C020122:estrone sulfotransferase; D000077185:Resveratrol