Liu Yitong, Santillo Michael F, Flynn Thomas J, Ferguson Martine S
Division of Toxicology, Office of Applied Research and Safety Assessment, Center for Food Safety and Applied Nutrition, US Food and Drug Administration, Laurel, MD, USA,
In Vitro Cell Dev Biol Anim. 2015 Apr;51(4):426-31. doi: 10.1007/s11626-014-9848-9. Epub 2014 Dec 6.
Genistein is a widely consumed phytoestrogen in dietary supplements and has been reported to play roles in both cancer prevention and promotion. These conflicting effects may be complicated by sex differences. Cytochrome P450 1A (CYP1A) participates in carcinogen activation and detoxification, and the enzyme may interact with genistein. Therefore, modulation of CYP1A by a combination of genistein and sex hormones could be responsible for sex differences related to cancer prevention and promotion. In the current study, a human liver cell line, HepG2/C3A, cultured in sex hormone-supplemented media was used to investigate the modulatory effect of genistein on CYP1A gene expression and activity. Genistein exerted both long-term (72 h) induction and short-term (immediate) inhibition of CYP1A activity in HepG2/C3A cells. In the long-term study, CYP1A gene expression and enzyme activity were induced to a greater extent in male hormone-supplemented cells than female ones. In the short-term study, CYP1A activity was inhibited more strongly by genistein in the male hormone-supplemented cells than in the female hormone-supplemented cells. These significant differences suggest that male hormones can modulate the effects of genistein on CYP1A gene expression and activity.
金雀异黄素是膳食补充剂中广泛食用的一种植物雌激素，据报道它在癌症预防和促进方面都发挥作用。这些相互矛盾的作用可能因性别差异而变得复杂。细胞色素P450 1A（CYP1A）参与致癌物的激活和解毒，并且该酶可能与金雀异黄素相互作用。因此，金雀异黄素与性激素联合对CYP1A的调节可能是导致癌症预防和促进相关性别差异的原因。在本研究中，使用在补充性激素的培养基中培养的人肝癌细胞系HepG2/C3A来研究金雀异黄素对CYP1A基因表达和活性的调节作用。金雀异黄素对HepG2/C3A细胞中CYP1A活性既有长期（72小时）诱导作用，也有短期（即时）抑制作用。在长期研究中，补充雄性激素的细胞中CYP1A基因表达和酶活性的诱导程度高于补充雌性激素的细胞。在短期研究中，金雀异黄素对补充雄性激素的细胞中CYP1A活性的抑制作用比对补充雌性激素的细胞更强。这些显著差异表明雄性激素可以调节金雀异黄素对CYP1A基因表达和活性的影响。
