The Red Wine Polyphenol Resveratrol Displays Bilevel Inhibition on Aromatase in Breast Cancer Cells

Abstract

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.

Use of Grape Polyphenols Against Carcinogenesis: Putative Molecular Mechanisms of Action Using In Vitro and In Vivo Test Systems

“…Kinetic analysis indicated that both competitive and noncompetitive inhibition might be involved. 21 The cell proliferation specifically induced by testosterone was significantly reduced by 10 lM resveratrol. In addition, 50 lM resveratrol significantly reduced the CYP19-encoding mRNA abundance.…”

“…In addition, 50 lM resveratrol significantly reduced the CYP19-encoding mRNA abundance. 21 Luciferase reporter gene assays revealed that resveratrol could repress the transcriptional control dictated by the promoter regulation. 21 In human fibrosarcoma cells, resveratrol was able to block adherence to endothelial cells in a dose-dependent manner.…”

“…21 Luciferase reporter gene assays revealed that resveratrol could repress the transcriptional control dictated by the promoter regulation. 21 In human fibrosarcoma cells, resveratrol was able to block adherence to endothelial cells in a dose-dependent manner. 22 To further elucidate the mechanisms of this resveratrolmediated blockade of tumor cell adhesion, the expression of the cell adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1, and Eselectin were examined.…”

Food Factors and Oxidative DNA Damage / DNA Repair Systems

“…Thus, anti-oxidant agents seem to play a key role in the beneficial effects of wine. It was also suggested that resveratrol could reduce the localized estrogen production that plays a crucial role in the development of breast cancer [32]. On the other hand, for alcoholic beverages other than wine, a cohort study suggested that alcohol (spirits and beer) consumption was associated with a decrease in the risk of renal cell carcinoma in male smokers [33].…”

Effect of vaginal gestrinone in Pentravan® on endometriosis patients using Mirena®: A preliminary report

“…Two polyphenols, Pinus pinaster extract and resveratrol, were used concomitantly [8]. These natural polyphenols are a complex mixture of flavonoids extracted from the bark of a pine tree (Pinus pinaster) or present in red wine (resveratrol), and are able to block both NF-Kappa.b and aromatase activity [9,10]. The effect of vaginal gestrinone associated with these natural polyphenols on aromatase expression in the endometrium of these patients was also investigated.…”