In the Journals

Resveratrol may contribute to breast cancer prevention

Resveratrol prevented the formation of estrogen-DNA adduct and neoplastic transformation in MCF-10F cells, which could avert the development of breast cancer, according to the results of a recent study.

The researchers at the University of Nebraska found resveratrol, a natural antioxidant, to have anticarcinogenic effects in diverse in vivo and in vitro systems.

Eleanor Rogan, MD, PhD, a professor at the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center, said the antioxidant, which appears naturally in red grapes and other plants and is sold as a dietary supplement, could thwart breast cancer before it starts.

“Resveratrol has the ability to prevent the first step that occurs when estrogen starts the process that leads to cancer by blocking the formation of the estrogen DNA adducts,” she said in a press release. “We believe that this could stop the whole progression that leads to breast cancer down the road.”

Cytochrome P450-mediated oxidation of catechol estrogens to quinines that react with DNA to form depurinating estrogen-DNA adducts may lead to genotoxicity. The researchers hypothesized that the resveratrol acts to regulate the dynamic balance of estrogen metabolism by regulating enzymes and chemically preventing estrogen metabolite formation in MCF-10F cells.

Using cells collected by the American Type Culture Collection, the study team showed a chemoprotective effect in resveratrol. The researchers stated that effect is caused by the antioxidant’s free radical scavenging ability, as well as its regulating role for phase-1 activating enzymes and phase-2 deactivating enzymes.

The researchers found that resveratrol suppressed the expression of cytochrome P450 and the formation of 2,3,7,8-tetrachlorodibenzo-p-dioxin. – by Jason Harris

Cancer Prev Res. 2008;1:135-145

PERSPECTIVE

The study by Lu et al in a human breast cell line focuses our attention on the pathways for metabolism of estrogen as a target for breast cancer prevention. In humans, 3,4 catechol estrogen quinone metabolites are formed by the metabolism of estradiol and estrone. These metabolites react with DNA to form specific adducts associated with increased mutation and initiation of the carcinogenic process. The catechol estrogen quinones can be inactivated by cytoprotective enzymes such as the glutathione S-transferases and quinone reductase. Therefore, agents such as resveratrol that may alter the balance between the formations of DNA adducts and the inactivation of catechol estrogen quinone metabolites in a favorable manner by suppressing estrogen metabolism or by inducing cytoprotective enzymes, as observed in this study, have the potential to prevent breast cancer. The results of this study in human breast epithelial cells are promising. They connect decreases in catechol estrogen DNA adducts with decreased estrogen-induced transformation in human cells. However, studies in humans are needed to confirm these initial findings prior to the use of resveratrol for breast cancer prevention.

– Kala Visvanathan, MD

Assistant Professor in Oncology at The Johns Hopkins School of Medicine

Resveratrol prevented the formation of estrogen-DNA adduct and neoplastic transformation in MCF-10F cells, which could avert the development of breast cancer, according to the results of a recent study.

The researchers at the University of Nebraska found resveratrol, a natural antioxidant, to have anticarcinogenic effects in diverse in vivo and in vitro systems.

Eleanor Rogan, MD, PhD, a professor at the Eppley Institute for Research in Cancer and Allied Diseases at the University of Nebraska Medical Center, said the antioxidant, which appears naturally in red grapes and other plants and is sold as a dietary supplement, could thwart breast cancer before it starts.

“Resveratrol has the ability to prevent the first step that occurs when estrogen starts the process that leads to cancer by blocking the formation of the estrogen DNA adducts,” she said in a press release. “We believe that this could stop the whole progression that leads to breast cancer down the road.”

Cytochrome P450-mediated oxidation of catechol estrogens to quinines that react with DNA to form depurinating estrogen-DNA adducts may lead to genotoxicity. The researchers hypothesized that the resveratrol acts to regulate the dynamic balance of estrogen metabolism by regulating enzymes and chemically preventing estrogen metabolite formation in MCF-10F cells.

Using cells collected by the American Type Culture Collection, the study team showed a chemoprotective effect in resveratrol. The researchers stated that effect is caused by the antioxidant’s free radical scavenging ability, as well as its regulating role for phase-1 activating enzymes and phase-2 deactivating enzymes.

The researchers found that resveratrol suppressed the expression of cytochrome P450 and the formation of 2,3,7,8-tetrachlorodibenzo-p-dioxin. – by Jason Harris

Cancer Prev Res. 2008;1:135-145

PERSPECTIVE

The study by Lu et al in a human breast cell line focuses our attention on the pathways for metabolism of estrogen as a target for breast cancer prevention. In humans, 3,4 catechol estrogen quinone metabolites are formed by the metabolism of estradiol and estrone. These metabolites react with DNA to form specific adducts associated with increased mutation and initiation of the carcinogenic process. The catechol estrogen quinones can be inactivated by cytoprotective enzymes such as the glutathione S-transferases and quinone reductase. Therefore, agents such as resveratrol that may alter the balance between the formations of DNA adducts and the inactivation of catechol estrogen quinone metabolites in a favorable manner by suppressing estrogen metabolism or by inducing cytoprotective enzymes, as observed in this study, have the potential to prevent breast cancer. The results of this study in human breast epithelial cells are promising. They connect decreases in catechol estrogen DNA adducts with decreased estrogen-induced transformation in human cells. However, studies in humans are needed to confirm these initial findings prior to the use of resveratrol for breast cancer prevention.

– Kala Visvanathan, MD

Assistant Professor in Oncology at The Johns Hopkins School of Medicine