5th May 03:40
Resveratrol (Red Wine), Testosterone, and Breast Cancer Cells (cancer estrogen breast cancer)
Toxicol Sci. 2006 Apr 11; [Epub ahead of print]
The Red Wine Polyphenol Resveratrol Displays BI-Level Inhibition on
Aromatase in Breast Cancer Cells.
Wang Y, Lee KW, Chan FL, Chen S, Leung LK.
Department of Biochemistry, The Chinese University of Hong Kong, Shatin,
N.T., HONG KONG.
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 a genuine interest to uncover an
aromatase-inhibitory compound from a dietary source. Resveratrol is a
polyphenolic compound that can be isolated from g**** 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 IC50 value of 25 microM. Kinetic
****ysis indicated that both competitive and non-competitive inhibition
might be involved. The administration of 10 nmol/l testosterone - a
substrate of aromatase - produced a 50% increase in 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.