Targets for the action of phytoestrogens in breast cancer - Focus on isoflavones and resveratrol

Experimental evidence reveals that phytoestrogens have many targets through which they inhibit growth of breast cancer cells. These targets include cyclins, inhibitors of cyclin-dependent kinases (p21/p27), the tumour-suppressor gene p53, and pro-apoptotic and anti-apoptotic genes including Bax and Blc-2. This review covers the experimental evidence for mechanisms through which isoflavones and resveratrol may inhibit the growth of breast cancer cells, including the action of phytoestrogens on estrogen receptors and the epigenome. Although there is much evidence revealing that phytoestrogens can inhibit or stimulate these targets involved in inhibiting the growth of breast cancer cells, there is a large discrepancy between the high-μmol L-1 doses required to observe such anti-tumorigenic effects, and the blood concentrations of unbound "free" phytoestrogens that would be achieved by dietary intake. It is suggested that more experiments investigating low-dose mixtures of phytoestrogens and chronic exposure to phytoestrogens - a closer model of dietary intake - are required to substantiate claims that phytoestrogens can protect against breast cancer. © Her Majesty the Queen in Right of United Kingdom 2014.