Volume 88, Issue 5, November (2002), pp. 439-441 © The Author 2002
doi:10.1079/BJN2002711

Medline/PubMed Citation | Related Articles in PubMed | Download to Citation Matcher  

Invited commentary

Mechanistic explanations for the chemopreventive action of soyabean isoflavones: reducing the possibilities

Dianne Ford
School of Cell and Molecular Biosciences, University of Newcastle, Kings Road, Newcastle UponTyne, NE1 7RU, UK

There is increasing evidence in favour of a link between diets high in soyabeans, a rich source of the isoflavones genistein and daidzein, and reduced incidence of colon cancer and hormone-dependent cancers, such as breast and prostate cancer (for review, see Bingham et al. 1998). A number of studies in animal models demonstrate a chemopreventive effect of soyabean and/or genistein. For example, dietary soyabean and genistein inhibited the growth of transplantable tumours in rats (Schleicher et al. 1999; Zhou et al. 1999) and dietary isoflavones were shown to reduce the induction of tumours in rats by chemical carcinogens (Onozawa et al. 1999).

The isoflavones are polyphenolic compounds with structural similarity to mammalian oestradiol and belong, therefore, to a family of compounds referred to as phyto-oestrogens. The reported effects of genistein on cells are wide-ranging and numerous. Actions potentially involved in the chemopreventive effect of genistein include effects mediated through binding to oestrogen receptors (ER) (Kuiper et al. 1997), inhibition of DNA topoisomerase (Markovits et al. 1989), antioxidant action (Wei et al. 1993; Suzuki et al. 2002) and effects on cell signalling pathways. The latter include inhibition of tyrosine-specific protein kinases (Akiyama et al. 1987), inhibition of epidermal growth factor-induced phosphatidylinositol turnover (Imoto et al. 1988), inhibition of nuclear factor-κ B activation (Davis et al. 1999) and stimulation of transforming growth factor β synthesis and/or release (Kim et al. 2001). Induction of apoptosis, well established as a response of cancer cells to genistein (Balabhadrapathruni et al. 2000; Salti et al. 2000), is a potential link between a number of these cellular effects and anti-cancer action. Oestrogen promotes breast-cell proliferation, possibly through reduced apoptosis, and is considered a risk factor for breast cancer (Nenci et al. 1988). Therefore, genistein-induced apoptosis in breast-cancer cells may be the result of antagonism of oestrogen effects at ER. Po et al. (2002) address this possibility in a study reported in the present issue of the British Journal of Nutrition.