Isoflavones and the prevention of breast and prostate cancer: new perspectives opened by nutrigenomics

Abstract

Epidemiological evidence together with preclinical data from animal and in vitro studies strongly support a correlation between soy isoflavone consumption and protection towards breast and prostate cancers. The biological processes modulated by isoflavones, and especially by genistein, have been extensively studied, yet without leading to a clear understanding of the cellular and molecular mechanisms of action involved. This review discusses the existing gaps in our knowledge and evaluates the potential of the new nutrigenomic approaches to improve the study of the molecular effects of isoflavones. Several issues need to be taken into account for the proper interpretation of the results already published for isoflavones. Too often knowledge on isoflavone bioavailability is not taken into account; supra-physiological doses are frequently used. Characterization of the individual variability as defined by the gut microflora composition and gene polymorphisms may also help to explain the discrepancies observed so far in the clinical studies. Finally, the complex inter-relations existing between tissues and cell types as well as cross-talks between metabolic and signalling pathways have been insufficiently considered. By appraising critically the abundant literature with these considerations in mind, the mechanisms of action that are the more likely to play a role in the preventive effects of isoflavones towards breast and prostate cancers are reviewed. Furthermore, the new perspectives opened by the use of genetic, transcriptomic, proteomic and metabolomic approaches are highlighted.

Novel approaches for analysing gut microbes and dietary polyphenols: challenges and opportunities

“…Though diversity analysis tools are now integrated into pipelines such as QIIME (Caporaso et al, 2010), processing these large datasets remains a challenge. Integrating the disparate information gained by these novel analytical platforms in a systems biology approach may lead to workable, testable hypotheses for the impact of polyphenols on the microbial composition and human health, and to the development of fundamental understanding of these complex systems (Steiner et al, 2008;. (Nadkarni et al, 2002) in a SHIME system fed (arrows) with 1000 mg tea polyphenols administered as either a single bolus or part of the daily feeding.…”

“…Many studies on polyphenols to date have focused on the bioactivities of one specific molecule in aglycone form, often at supraphysiological doses, whereas foods contain complex, often poorly characterized mixtures with multiple additive or interfering activities (Steiner et al, 2008). Furthermore, recent human studies indicate that plasma concentrations and urinary excretions of microbial metabolites can exceed those of host origin, especially for polyphenols that are not easily absorbed in the upper gastro-intestinal tract and persist to the colon (Manach et al, 2009;van Dorsten et al, 2010).…”

Role of Metabolism in the Effects of Genistein and Its Phase II Conjugates on the Growth of Human Breast Cell Lines

“…Isoflavones including genistein have been reported to exert purported health benefits in aging-related and hormone-dependent disorders as well as cardiovascular diseases (1,2). Isoflavones, especially genistein, are thought to be responsible for the cancer prevention effects of soy and soy products (3)(4)(5). Proposed anticancer mechanisms of action include modulation of estrogen receptor (ER) signaling as a partial agonist of ERα and β (6), downregulation of protein kinases and DNA topoisomerase (7), induction of early mammary cell differentiation (8), inhibition of angiogenesis (9), and modulation of intracellular enzyme activities (10).…”

Dietary Manipulation for Therapeutic Effect in Prostate Cancer

“…Pharmacogenomic work suggests that the reduction in risk of prostate cancer may be positively associated with a greater ability to produce equol from other isoflavones (Akaza et al, 2002(Akaza et al, , 2004. "Nutrigenomic" factors may therefore play an important part in predicting those who might benefit from phytoestrogen supplementation (Steiner et al, 2008).…”