Study Probes Resveratrol's Anti-Cancer Activities
Antioxidant regulated estrogen-metabolizing enzymes, prevented formation of DNA adducts
THURSDAY, July 10 (HealthDay News) -- Resveratrol, an antioxidant found in grapes and other plant foods, may inhibit breast cancer initiation through its actions in the estrogen genotoxicity pathway, according to research published in the July issue of Cancer Prevention Research.
Fang Lu, Ph.D., of the University of Nebraska Medical Center in Omaha, and colleagues used MCF-10F human breast epithelial cells to investigate the effects of resveratrol on breast cancer initiation.
The investigators found that resveratrol could inhibit CYP1B1 (cytochrome P450 1B1) expression induced by TCDD (2,3,7,8-Tetrachlorodibenzo-p-dioxin) in cytoplasm and to a lesser degree in the nucleus. Resveratrol also induced the expression of NQO1 (NAD(P)H quinone oxidoreductase 1) proteins two- to threefold in a dose- and time-dependent manner. High CYP1B1 and low NQO1 activity appear to be linked to elevated risk of breast cancer, the authors write. They also found that resveratrol decreased estrogen metabolism in the MCF-10F cells and inhibited transformation of these cells by estradiol and estradiol plus TCDD.
"Based on these studies, in which resveratrol regulated estrogen-metabolizing enzymes, decreased estrogen metabolism, prevented DNA adduct formation, and suppressed estrogen-induced malignant transformation, we conclude that enhancing estrogen metabolism (in this case, by TCDD-induced CYP1B1) to increase formation of depurinating DNA adducts may play a major role in breast cancer initiation. Resveratrol may act as a potential chemopreventive agent against estrogen-initiated breast cancer by blocking most of the critical steps in the estrogen genotoxicity pathway," the authors write.