INDUCTION OF NADPH-QUINONE REDUCTASE BY DIETARY PHYTOESTROGENS IN COLONIC COLO205 CELLS

Phytoestrogens are a group of naturally occurring diphenolic compounds present in legumes, whole grains, fruits, and vegetables. High consum ption of phytoestrogen-rich foods has been linked to a reduced inciden ce of cancers at many sites. A potential mechanism of dietary anticarc inogenesis involves the induction of detoxifying phase II enzymes such as NADPH:quinone reductase (QR). This study, therefore, examined the ability of six prominent phytoestrogens to affect cellular expression of QR in colonic cells. Colo205 cells were cocultured with various con centrations (0.001 to 10.0 mu M) of each phytoestrogen, and then were assessed for cytosolic QR activity, cell growth, and QR mRNA expressio n. A maximum of 6- to 8-fold induction of QR activity was observed for both enterolactone and genistein, although at high concentrations the y showed an adverse effect upon cell growth. The concentrations requir ed to double the specific activity of QR for enterolactone and geniste in were about 0.04 and 0.14 mu M, respectively. A 2- to 3-fold increas e of QR specific activity was found with either biochanin A (1.1 mu M) or coumestrol (12.0 mu M) treatments. No significant effects were fou nd for daidzein or formononetin treatments. QR induction was further c onfirmed by using reverse transcription-polymerase chain reaction (RT- PCR) techniques to measure mRNA expression. A significant correlation between the expression of QR mRNA and the corresponding QR activity wa s-observed (r = 0.76, P < 0.001). The results demonstrated that certai n dietary phytoestrogens are capable of QR induction in Colo205 cells by promoting QR mRNA expression, and suggest a novel mechanism by whic h dietary phytoestrogens may be implicated in colorectal cancer chemop revention. (C) 1998 Elsevier Science Inc.