The most recent findings on soy and isoflavones were presented in Washington DC on the occasion of the 9th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment (October 16-19, 2010). A major part of the topics was dedicated to safety and health benefits in menopausal women, and to the issue of soy and breast cancer.
Equol is an isoflavone metabolite formed by gut bacteria from daidzein. It is a chiral molecule and may therefore occur in two enantiomeric structures, the natural S-(-)-form, and the synthetic R-(+)-form. As Prof. Stephen Barnes (University of Alabama, USA) outlined, animals such as rodents are highly efficient equol producers: in their blood equol predominates over genistein or daidzein with 4-8 times higher concentrations (Barnes 2010). In contrast, humans are relatively poor equol producers: only 30-50 % of humans are capable of equol producing, and therefore genistein usually prevails over equol in the blood.
Like genistein, equol binds to ER-β. It was recently demonstrated that isoflavones and tamoxifen occupy different binding sites at the ER-β (Dai et al. 2009). S-Equol is a strong agonist at the ER-β, and the natural enantiomer has about 20 times stronger receptor effects in cell models than the synthetic R-equol. Daidzein as such is much less effective und requires conversion to equol to achieve its full strength. Strangely, daidzein and equol do not promote breast cancer cell proliferation in the model of the xenotransplanted ovariectomized rodent (Ju et al. 2006). This discrepancy is a further indication that no valid conclusions may be drawn from this model for the extrapolation to the situation in humans. With respect to cancer preventive effects other mechanisms of action need to be taken into account, i.e., the inhibition of the formation of metastases, the inhibition of cell signalling mediators such as TNF-α, or the inhibition of the expression of genes such as PPARγ (Chacko et al. 2005; Chacko et al. 2007).
A new area of research where isoflavones may contribute to overall cancer-protective effects is the effect on micro-RNA, which is a regulator of post-translation protein biosynthesis. Up- or down-regulation of specific types of micro-RNA has been associated with cancer growth or inhibition (Satzger et al. 2010; Zaman et al. 2010), and recent research has found effects of genistein on different types of micro-RNA associated with the inhibition of cancer such as melanoma (Sun et al. 2009), prostate cancer (Majid et al. 2010) or pancreas cancer (Li et al. 2010).
References
Barnes, S. (2010). Brief introduction to equol. 9th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment, Washington DC, 16-19 October.
