Changes in gene expressions elicited by physiological concentrations of genistein on human endometrial cancer cells

Abstract

The incidence of hormone-related diseases such as prostatic, breast, ovarian, and endometrial cancer is lower in Asian populations compared to Western countries. High consumption of soybean products that are rich in phytoestrogens, predominantly genistein, is postulated to be responsible for the lower incidence of hormone-related disease, although the mechanism through which this effect might be mediated is unclear. In this study, microarray analysis was used to identify the changes in gene expression elicited by treatment of the human endometrial cancer cell line, Ishikawa, with genistein at both physiologically achievable and supraphysiological concentrations. Genistein treatment at 5 microM concentration induced multiple changes in gene expression including some implicated in oncogenesis. In contrast, treatment with a supraphysiological concentration of genistein predominantly activated stress response genes and showed very limited overlap with the genes regulated at lower concentrations. Of the genes regulated by genistein, 9.3% were also regulated by 17beta-estradiol suggesting that genistein exerts its response via the estrogen pathway. These results indicate that at physiological concentrations, genistein is able to elicit pleiotropic effects on a variety of pathways believed to be involved in tumorigenesis. Supraphysiological concentrations of genistein, such as those used in many previous studies, elicit changes in gene expression that are unlikely to occur in vivo.

Functional genomics of endothelial cells treated with anti-angiogenic or angiopreventive drugs

“…Similar effects have been shown in several others cellular systems [194][195][196] and in mice [197][198][199]. Genistein effects clearly depend on the dosage with pro-estrogenic activities being dominant at lower and anti-apoptotic activities at higher concentrations [200], similar observations have been reported by Konstantakopoulos et al [201]. The phytoestrogens resveratrol and quercetin present in the Mediterranean diet have also been reported to exert anti-angiogenic activities through the inhibition of endothelial cell proliferation yet only at high concentrations [202].…”

Naringenin and 17β‐estradiol coadministration prevents hormone‐induced human cancer cell growth

“…These findings are relevant in view of the possible action of ERβ as a tumor suppressor. In search for agents that would be useful in preventing and treating E2‐dependent cancer, the interest in flavonoids has increased markedly (5, 24–30). In fact, contrary to E2, flavonoids bind to ERβ with up to five times higher affinities compared with ERα (31, 32).…”

Global gene expression profiles induced by phytoestrogens in human breast cancer cells

“…This difference has often been attributed to a much higher dietary intake of soy phytoestrogens (Konstantakopoulos et al 2006, Martinez et al 2006, McCarty 2006, Messina et al 2006. However, despite the large amount of research conducted in the last years, no clear consensus has emerged regarding the preventive action of phytoestrogens against cancer.…”