Yeh Jan-Ying, Ou Bor-Rung, Liang Yu-Chuan, Burchfiel Joel, Butler Judy A, Forsberg Neil E, Whanger Philip D
Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan, ROC.
Biometals. 2006 Dec;19(6):611-21. doi: 10.1007/s10534-006-0007-y. Epub 2006 Sep 1.
The objective of this study was to investigate the differential effects of various selenium (Se) compounds and Se-enriched broccoli extracts on cell proliferation and the possible mechanism responsible for the Se-induced growth inhibition. C6 rat glial cells were incubated with graded concentrations up to 1000 nM of selenite, selenate, selenomethionine (SeM), Se-methyl-selenocysteine (SeMCys), high-Se broccoli (H-SeB) extract or low-Se broccoli (L-SeB) extract for 24 and 48 h. MTT results indicated that all Se sources and levels examined inhibited C6 cell proliferation at 48 h. The results from cell cycle progression and apoptosis analysis indicated that SeM, SeMCys, H-SeB or L-SeB treatments at the concentration of 1000 nM reduced the cell population in G(0)/G(1) phase, but induced G(2)/M phase arrest and increased apoptosis and secondary necrosis in C6 cells at 24 h. The populations of apoptotic cells and secondary necrotic cells were increased by all Se sources examined. The COMET assay indicated that there was no significant DNA single-strand break found for all Se treatments in C6 cells for 48 h. In addition, the Se-induced proliferation inhibition may involve a hydrogen peroxide (H(2)O(2))-dependent mechanism with elevated cellular glutathione peroxidase (cGPX) activity. Both H-SeB and L-SeB inhibited C6 cell proliferation but H-SeB was less inhibitory than L-SeB. The proliferation inhibition by H-SeB in C6 cells is apparently related to the increased H(2)O(2) with the elevated cGPX activity, but the inhibition by L-SeB was H(2)O(2)-independent without change in cGPX activity.
本研究的目的是调查各种硒（Se）化合物和富硒西兰花提取物对细胞增殖的不同影响以及硒诱导生长抑制的可能机制。将C6大鼠神经胶质细胞与浓度高达1000 nM的亚硒酸盐、硒酸盐、硒代蛋氨酸（SeM）、硒甲基硒代半胱氨酸（SeMCys）、高硒西兰花（H-SeB）提取物或低硒西兰花（L-SeB）提取物进行梯度孵育24小时和48小时。MTT结果表明，所有检测的硒源和水平在48小时时均抑制C6细胞增殖。细胞周期进程和凋亡分析结果表明，1000 nM浓度的SeM、SeMCys、H-SeB或L-SeB处理在24小时时减少了G(0)/G(1)期的细胞数量，但诱导了G(2)/M期阻滞，并增加了C6细胞的凋亡和继发性坏死。所有检测的硒源均增加了凋亡细胞和继发性坏死细胞的数量。彗星试验表明，在48小时时，所有硒处理在C6细胞中均未发现明显的DNA单链断裂。此外，硒诱导的增殖抑制可能涉及依赖过氧化氢（H(2)O(2)）的机制，细胞谷胱甘肽过氧化物酶（cGPX）活性升高。H-SeB和L-SeB均抑制C6细胞增殖，但H-SeB的抑制作用小于L-SeB。H-SeB对C6细胞的增殖抑制显然与H(2)O(2)增加和cGPX活性升高有关，但L-SeB的抑制作用与H(2)O(2)无关，cGPX活性无变化。
