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 cellculture 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.Soya isoflavones: Breast cancer: Cell-culture models

Genistein protects against polycyclic aromatic hydrocarbon-induced oxidative DNA damage in non-cancerous breast cells MCF-10A

“…The former study measured 8-oxoG in calf thymus DNA generated from incubating with orobol, NADH and Cu (II). Genistein can also act on oestrogen receptors and apoptosis in breast cancer cells as reviewed by Leung et al ( 23 ) .…”

Editorial

“…In the last issue, Hall et al (2005) discussed the role of isoflavones in endothelial function. In this issue, Cassidy (2005) discusses the beneficial effects of isoflavones as an alternative to oestrogen replacement therapy to promote health in peri-and post-menopausal women, while Leung et al (2005) discuss the protective effects of isoflavones with respect to breast cancer.…”

“…One approach to determine relationships between diet and health is to identify individual foods or nutrients that may confer protection -see, for example, the papers by Cooper et al (2004) on wine polyphenols, and Tripoli et al (2005) on polyphenols in olive oil, as well as the papers in this issue and the last on isoflavones (Cassidy, 2005;Hall et al 2005;Leung et al 2005). Michels & Schulze (2005) discuss the problems inherent in this type of research, and ask whether analysis of dietary patterns may provide more useful information.…”