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 consumption of phytoestrogen-rich foods has been linked to a reduced incidence of cancers at many sites. A potential mechanism of dietary anticarcinogenesis 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 concentrations (0.001 to 10.0 microM) of each phytoestrogen, and then were assessed for cytosolic QR activity, cell growth, and QR mRNA expression. A maximum of 6- to 8-fold induction of QR activity was observed for both enterolactone and genistein, although at high concentrations they showed an adverse effect upon cell growth. The concentrations required to double the specific activity of QR for enterolactone and genistein were about 0.04 and 0.14 microM, respectively. A 2- to 3-fold increase of QR specific activity was found with either biochanin A (1.1 microM) or coumestrol (12.0 microM) treatments. No significant effects were found for daidzein or formononetin treatments. QR induction was further confirmed 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 was observed (r = 0.76, P < 0.001). The results demonstrated that certain dietary phytoestrogens are capable of QR induction in Colo205 cells by promoting QR mRNA expression, and suggest a novel mechanism by which dietary phytoestrogens may be implicated in colorectal cancer chemoprevention.
Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA. wwang@iastate.edu
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D001483:Base Sequence; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D017931:DNA Primers; D004032:Diet; D004790:Enzyme Induction; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000235:genetics; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D048789:Phytoestrogens; D028321:Plant Preparations; D012333:RNA, Messenger; D016660:NAD(P)H Dehydrogenase (Quinone)