The longer women are exposed to estrogens including the estrogens in traditional hormone replacement therapy (HRT) the higher their risk of developing hormone-dependent cancers.  As a result, women are turning to botanical dietary supplements as natural and potentially safer alternatives to HRT despite the lack of efficacy/toxicity data.  Estrogens are metabolized to carcinogenic 4-hydroxy metabolites, which are further oxidized to o-quinones which can covalently modify cellular macromolecules including DNA as well as generate oxidative stress all of which could lead to genetic mutations and malignant transformation.  We hypothesize that botanical dietary supplements could protect women from estrogen chemical carcinogenesis in a variety of ways including modulation of P450 1B1 and P450 1A1, induction of detoxification enzymes including NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTs), as well as have antioxidant effects.  The botanical dietary supplements hops and licorice and their bioactive compounds xanthohumol and isoliquiritigenin, respectively are particularly effective at NQO1 induction in normal breast epithelial cells (MCF-10A).  Induction of the antioxidant response element (ARE) in HepG2 cells implied the Keap1/Nrf2 pathway as the underlying mechanism.  These botanicals also cause dose-dependent reduction in catechol estrogen levels in MCF-10A cells.  Finally, we have recently determined that inflammation could play a major role in chemical estrogen carcinogenesis through inflammation-driven P450 1B1 expression leading to enhanced estrogen quinone formation.  As a result, the anti-inflammatory properties of these popular botanical dietary supplements used for women's health may represent additional chemopreventive mechanisms.  Supported by P50 AT00155 provided by ODS and NCCAM.

Prevention of estrogen carcinogenesis by botanical dietary supplements for women's health

248th National Meeting (2014)

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