International Journal of Oncology, 2013, 42(2):733-740(8).

Genistein, a soy phytoestrogen, prevents the growth of BG-1 ovarian cancer cells induced by 17β-estradiol or bisphenol A via the inhibition of cell cycle progression

Kyung-A Hwang, Nam-Hee Kang, Bo-Rim Yi, et al

Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea

An endocrine disrupting chemical (EDC) is a global health concern. In this study, we examined the effects of genistein (GEN) on bisphenol A (BPA) or 17β-estradiol (E2)-induced cell growth and gene alterations of BG-1 ovarian cancer cells expressing estrogen receptors (ERs). In an in vitro cell viability assay, E2 or BPA significantly increased the growth of BG-1 cells. This increased proliferative activity was reversed by treatment with ICI 182,780, a well-known ER antagonist, while cell proliferation was further promoted in the presence of propyl pyrazole triol (PPT), an ERα agonist. These results imply that cell proliferation increased by E2 or BPA was mediated by ERs, particularly ERα. BPA clearly acted as a xenoestrogen in BG-1 ovarian cancer cells by mimicking E2 action. In contrast, GEN effectively suppressed BG-1 cell proliferation promoted by E2 or BPA by inhibiting cell cycle progression. E2 and BPA increased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition. They also decreased the expression of p21, a potent cyclin-dependent kinase (CDK) inhibitor that arrests the cell cycle in G1 phase, and promoted the proliferation of BG-1 cells. As shown by its repressive effect on cell growth, GEN decreased the expression of cyclin D1 augmented by E2 or BPA. On the other hand, GEN increased the p21 expression downregulated by E2 or BPA. Collectively, our findings suggest that GEN, a dietary phytoestrogen, has an inhibitory effect on the growth of estrogen-dependent cancers promoted by E2 or BPA.

希腊《国际肿瘤学杂志》，2013年2月

金雀异黄素，一种 大豆植物雌激素，通过抑制细胞周期进程可以阻止17β- 雌二醇或双酚 A诱导的BG-1 卵巢癌细胞生长

黄京和，康南熙，尹波环，等

大韩民国清州忠北国立大学兽医学院兽医生化和免疫学实验室

内分泌干扰化学 (EDC) 是一个全球性的健康问题。在此研究中，我们研究金雀异黄素(GEN) 对双酚 A (BPA) 或 17 β-雌二醇 (E2)-诱导BG-1 卵巢癌细胞的细胞生长和基因改变雌激素受体 (ERs)的表达。在一项体外细胞活性实验中，E2 或双酚 A 显著增加了 BG-1 细胞的生长。这增加的增殖活性可以通过 ICI 182,780，一种出名的 ER 拮抗剂，治疗逆转，而细胞增殖得到进一步促进在丙基吡唑醇 (PPT)，一种ERα 受体激动剂的作用下。这些结果意味着E2 或双酚 A对细胞增殖的促进作用由ERs，特别是ERα 调节。通过模仿 E2 的活动，BPA明显地充当 了BG-1 卵巢癌细胞中的外源性雌激素。相比之下，GEN通过抑制细胞周期进程有效抑制了由E2 或者BPA促进的BG-1 细胞的增殖。E2 和BPA 提高了细胞周期蛋白 D1的表达，负责 G1/S 细胞周期过渡的一个因素。它们还降低 了p21的表达，一种强效的细胞周期蛋白依赖性激酶 (CDK) 抑制剂，在 G1 期阻滞细胞周期并促进BG-1细胞的增殖。如其抑制细胞生长作用所示，GEN降低了由E2 或BPA促进的细胞周期蛋白 D1的表达。另一方面，GEN提高了由 E2 或BPA下调的p21 的表达。总之，我们的研究结果表明，GEN，一种膳食植物雌激素，对 E2 或BPA 促进的雌激素依赖性肿瘤生长具有抑制作用。