The red wine polyphenol resveratrol displays bilevel inhibition on aromatase in breast cancer cells.

Estrogen plays a crucial role in the development of breast cancer, and the inhibition of estrogen synthesis has been an important target for the prevention and treatment of this disease. The rate-limiting reaction of the hormone biosynthesis is catalyzed by cytochrome P450 (CYP) 19 enzyme or aromatase. It has been of genuine interest to uncover an aromatase-inhibitory compound from a dietary source. Resveratrol is a polyphenolic compound that can be isolated from grape peel. Because of its structural resemblance to estrogen, resveratrol's agonistic and antagonistic properties on estrogen receptor have been examined and demonstrated. In the present study, the effect of resveratrol on the expression and enzyme activity of aromatase was investigated. By assaying on MCF-7 cells stably transfected with CYP19 (MCF-7aro cells), resveratrol inhibited the aromatase activity with an IC(50) value of 25 microM. Kinetic analysis indicated that both competitive and noncompetitive inhibition might be involved. The administration of 10 nmol/l testosterone-a substrate of aromatase-produced a 50% increase in the MCF-7aro cell number. This cell proliferation specifically induced by testosterone was significantly reduced by 10 microM resveratrol. In addition, 50 microM resveratrol significantly reduced the CYP19-encoding mRNA abundance in SK-BR-3 cells. The transcriptional control of CYP19 gene is tissue specific, and promoter regions I.3 and II have previously been shown to be responsible for CYP19 expression in breast cancer cells. Luciferase reporter gene assays revealed that resveratrol could repress the transcriptional control dictated by the promoter regulation. The present study illustrated that pharmacological dosage of resveratrol inhibited aromatase at both the enzyme and mRNA levels.

18ß-glycyrrhetinic acid induces UDP-glucuronosyltransferase in rats.

UDP-glucuronosyltransferase (UDP) catalyzes a broad spectrum of endobiotic and xenobiotics. It is the isoform of the UGT1 family, which are made from the complex gene locus by an alternative combination of one of the unique first exons with the commonly used exons. UDP is believed to be involved in cellular activity and signaling process associated with detoxification. In this study, rats were orally administered with 18ß-glycyrrhetinic acid (GA) for four weeks before rats were sacrificed. The mRNA was extracted from the liver and cDNA was prepared by reverse transcription method. By PCR and Northern blot analysis, UGT1A8 mRNA level was found to be increased in the treatment group (P < 0.05). The results showed that the mRNA expression of UGT1A8 could be induced both by GA and the licorice extract. GA was identified to be the active component of the aqueous extract of licorice responsible for induction of UGT1A8 in the rat liver. The results suggest a transcriptional control of the UGT1A8 synthesis can be modulated by phytochemicals in the rat liver. The increased UDP activity could enhance detoxification of toxicants.