Sinha R, Said T K, Medina D
Department of Cell Biology, Baylor College of Medicine, TX 77030, USA.
Cancer Lett. 1996 Oct 22;107(2):277-84. doi: 10.1016/0304-3835(96)04373-x.
Selenium, both organic and inorganic forms, inhibit mammary tumorigenesis in vivo and mammary cell growth in vitro. In the present study, sodium selenite was compared to methylselenocysteine (MSC) for their individual effects on cell growth, cdc2/cdk2 kinase activities and the levels of cyclins D1, E and A bound to cdk2 in a mouse mammary epithelial cell culture model. Selenite arrested the growth of cells in S-G2-M phase in contrast to MSC which arrested or delayed the cells in G1. In MSC-treated cells there was a 57% drop in the cdk2 kinase activity accompanied by a 73.5% decrease in cyclin E-cdk2 content as compared to the control cells. Selenite treatment increased the cdk2 kinase activity by 30% without any appreciable change in either of the cyclins D1, E or A bound to cdk2 when compared to the control cells. These data support the hypothesis that selenite and MSC have distinct modes of action in the inhibition of cell growth in vitro. Selenite has a strong genotoxic effect on the tumor cells; in contrast, MSC appears to inhibit cell growth via specific inhibition of cell cycle regulatory proteins.
有机和无机形式的硒均能在体内抑制乳腺肿瘤发生，在体外抑制乳腺细胞生长。在本研究中，在小鼠乳腺上皮细胞培养模型中，比较了亚硒酸钠和甲基硒代半胱氨酸（MSC）对细胞生长、cdc2/cdk2激酶活性以及与cdk2结合的细胞周期蛋白D1、E和A水平的各自影响。与使细胞在G1期停滞或延迟的MSC相反，亚硒酸钠使细胞在S-G2-M期的生长停滞。与对照细胞相比，在经MSC处理的细胞中，cdk2激酶活性下降了57%，同时细胞周期蛋白E-cdk2含量减少了73.5%。与对照细胞相比，亚硒酸钠处理使cdk2激酶活性增加了30%，而与cdk2结合的细胞周期蛋白D1、E或A均无明显变化。这些数据支持以下假设：亚硒酸钠和MSC在体外抑制细胞生长方面具有不同的作用模式。亚硒酸钠对肿瘤细胞具有很强的基因毒性作用；相比之下，MSC似乎通过特异性抑制细胞周期调节蛋白来抑制细胞生长。
