抄録
Resveratrol (trans-3,4',5-trihydroxystilbene, RES), a phytoestrogen, exists in grape skin, peanuts, and red wine, known for beneficial material, due to its antioxidant, anti-inflammatory effects. Endocrine disrupting chemicals (EDCs) appear to promote the development and progression of the estrogen dependant cancers. In this study, we evaluated the inhibitory effect of RES on the cell growth and progression induced by various EDCs in BG-1 ovarian cancer cells expressing estrogen receptors (ERs). The various EDCs, i.e., bisphenol A (BPA), nonylphenol (NP), octylphenol (OP), methoxychlor (MXC), and hexabromocyclododecane (HBCD) were employed in this study. In the in vitro experiments, treatments of BG-1 cells with E2, BPA, NP, OP, MXC, or HBCD resulted in an increase of their growth. The treatment of BG-1 cells with ICI 182,780, a well known antagonist of ERs, reversed EDCs induced cell growth in these cells, indicating that their growth stimulatory effect is mediated through ERs. In addition, we evaluated the effect of RES in the presence of other EDCs by MTT assay. As a result, increased cell viability induced by these EDCs. On the other hand, cell viability of co-cultured with RES was decreased. In addition, we further examined the regulation of cell cycle dependent genes by RT-PCR in E2, BPA, or NP and co-treatment of RES and each EDC. Concretely, the treatment with each EDC only decreased the gene expression of p21 and increased the expression of cell cycle-dependent kinase 2 (CDK2). However, co-treatment with RES and one of EDCs resulted in the increased gene expressions of p21 and the decreased expression of CDK2. Cyclin D1 was increased by downregulating p21 when only treated with each EDC in the absence of RES, while co-treatment with RES and each EDC decreased the gene expression of cyclin D1 by upregulating p21. Taken together, these results indicate that RES appear to be Cyclin D1 and CDK2 inhibitor and is responsible for the cell cycle arrest at G1 phase. In addition, when co-treated with each EDC, RES increased the expressions of p21 and resulted in the growth inhibition of BG-1 ovarian cancer cells. As a result, we confirmed the cell growth inhibitory effect of RES, a dietary phytoestrogen, on the estrogen-dependant ovarian cancer cells prompted by EDCs. [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).]
