A phytoestrogen, genistein, reversed 17 β-estradiol or bisphenol A-induced cell growth via downregulation of the cell cycle progression in BG-1 ovarian cancer cells
K. Hwang, N. Kang & K. Choi
One of estrogens, 17b-estradiol (E2), is a pleiotropic hormone that regulates the growth and differentiation of many tissues and also acts as a mitogen that promotes the development and proliferation of hormone-responsive cancers. Bisphenol A (BPA) is a widely used industrial compound and classified as one of endocrine disrupting chemicals (EDCs) and especially a xenoestrogen that imitates estrogen in living organisms. In this study, we examined the effect of a phytoestrogen, genistein, on the cell growth of BG-1 ovarian cancer cells expressing estrogen receptors (ERs) caused by E2 and BPA. In the cell proliferation test in vitro, E2 or BPA increased the growth of the BG-1 ovarian cancer cells expressing ERs. Their proliferation activity was reversed by the treatment of ICI 182,780, a well-known antagonist of ERs, which demonstrates that the cell proliferation by E2 or BPA is mediated by ERs and BPA certainly acts as a xenoestrogen in the BG-1 ovarian cancer cells. Genistein, an isoflavone, is one of phytoestrogens that are plant-derived, naturally occurring, and dietary xenoestrogens and influences multiple biochemical functions. In this study, genistein effectively suppressed the BG-1 cell proliferation induced by E2 or BPA by adversely down regulating the cell cycle progression that was upregulated by E2 or BPA. Concretely, E2 or BPA decreased the gene expression of p21, which is a potent cyclin-dependent kinase (Cdk) inhibitor and responsible for the cell cycle arrest at G1 phase, to proliferate the BG-1 cells. On the other hand, genistein upregulated the expression of p21 gene cultured in the presence of E2 or BPA, leading to the growth inhibition of the BG-1 cells. Also, the alteration of p21 gene expression by E2, BPA, or genistein affected the expression of its downstream genes of cell cycle, cyclin D1 and Cdk-4. Taken together from these results, we may suggest an anticancer effect of genistein, a dietary phytoestrogen, on the estrogen-dependant cancers like ovarian cancer prompted by E2 or BPA. [This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of Korea government (no. 2011-0015385)]
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.