Dietary soya isoflavones and breast carcinogenesis: a perspective from a cell-culture model

Abstract

Southeast Asian women have a lower incidence of breast cancer than their counterparts in the West. Epidemiological studies have indicated that soya consumption may be a contributing factor. Carcinogenesis is a process involving multiple stages. The present review attempts to fit the cellular mechanisms attributed to soya isoflavones into these different stages. Many cell-culture studies have reported the growth-inhibitory effect of soya isoflavones; however, with the non-physiological concentrations employed in these studies it would be difficult to explain the protection mechanisms observed in epidemiological studies. Our laboratory has previously found that genistein inhibits cytochrome P450 (CYP)1A1 and CYP1B1. The inhibition implies that soya consumption may have the potential to prevent chemical carcinogenesis. The preferential inhibition of CYP1B1 may also block the oestrogen-initiated carcinogenesis. The antagonism of oestrogen receptor (ER) binding can affect the cell-proliferative phase, which is likely to be important in the promotion stage of breast cancer. Since our laboratory and others have indicated that genistein at physiological concentrations has no effect on the downstream activities of ER binding, the antagonism of ER is not likely to be a contributing factor in the disease prevention. Moreover, soya isoflavones cannot inhibit aromatase (CYP19), which is the enzyme responsible for oestrogen synthesis. In the present review various cellular activities altered by soya isoflavones are discussed.