Journal Article

The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer

Nadine M. Brown, Carrie A. Belles, Stephanie L. Lindley, Linda D. Zimmer-Nechemias, Xueheng Zhao, David P. Witte, Mi-Ok Kim and Kenneth D.R. Setchell

in Carcinogenesis

Volume 31, issue 5, pages 886-893
Published in print May 2010 | ISSN: 0143-3334
Published online January 2010 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgq025
The chemopreventive action of equol enantiomers in a chemically induced animal model of breast cancer

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We describe for the first time the chemopreventive effects of S-(−)equol and R-(+)equol, diastereoisomers with contrasting affinities for estrogen receptors (ERs). S-(−)equol, a ligand for ERβ, is an intestinally derived metabolite formed by many humans and by rodents consuming diets containing soy isoflavones. Whether the well-documented chemopreventive effect of a soy diet could be explained by equol's action was unclear because neither diastereoisomers had been tested in animal models of chemoprevention. Sprague–Dawley rats (n = 40–41 per group) were fed a soy-free AIN-93G diet or an AIN-93G diet supplemented with 250 mg/kg of S-(−)equol or R-(+)equol beginning day 35. On day 50, mammary tumors were induced by dimethylbenz[a]anthracene and thereafter, animals were palpated for number and location of tumors. On day 190, animals were killed and mammary tumors were removed and verified by histology, and the degree of invasiveness and differentiation was determined. S-(−)equol and R-(+)equol plasma concentrations measured on days 35, 100 and 190 by tandem mass spectrometry confirmed diet compliance and no biotransformation of either diastereoisomer. In this model, S-(−)equol had no chemopreventive action, nor was it stimulatory. In contrast, R-(+)equol compared with Controls reduced palpable tumors (P = 0.002), resulted in 43% fewer tumors (P = 0.004), increased tumor latency (88.5 versus 66 days, P = 0.003), and tumors were less invasive but showed no difference in pattern grade or mitosis. Both enantiomers had no effect on absolute uterine weight but caused a significant reduction in body weight gain. In conclusion, the novel finding that the unnatural enantiomer, R-(+)equol, was potently chemopreventive warrants investigation of its potential for breast cancer prevention and treatment.

Journal Article.  7370 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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