Chen Tianfeng, Wong Yum-Shing
Department of Biology, State Key Laboratory China for Agrobiotechnology and Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Hong Kong, China.
J Agric Food Chem. 2008 Nov 26;56(22):10574-81. doi: 10.1021/jf802125t.
Selenocystine (SeC) is a nutritionally available selenoamino acid with selective anticancer effects on a number of human cancer cell lines. The present study shows that SeC inhibited the proliferation of human breast adenocarcinoma MCF-7 cells in a time- and dose-dependent manner, through the induction of cell cycle arrest and apoptotic cell death. SeC-induced S-phase arrest was associated with a marked decrease in the protein expression of cyclins A, D1, and D3 and cyclin-dependent kinases (CDKs) 4 and 6, with concomitant induction of p21waf1/Cip1, p27Kip1, and p53. Exposure of MCF-7 cells to SeC resulted in apoptosis as evidenced by caspase activation, PARP cleavage, and DNA fragmentation. SeC treatment also triggered the activation of JNK, p38 MAPK, ERK, and Akt. Inhibitors of ERK (U0126) and Akt (LY294002), but not JNK (SP600125) and p38 MAPK (SB203580), suppressed SeC-induced S-phase arrest and apoptosis in MCF-7 cells. The findings establish a mechanistic link between the PI3K/Akt pathway, MAPK pathway, and SeC-induced cell cycle arrest and apoptosis in MCF-7 cells.
硒代胱氨酸（SeC）是一种可作为营养物质利用的含硒氨基酸，对多种人类癌细胞系具有选择性抗癌作用。本研究表明，SeC通过诱导细胞周期停滞和凋亡性细胞死亡，以时间和剂量依赖性方式抑制人乳腺腺癌MCF-7细胞的增殖。SeC诱导的S期停滞与细胞周期蛋白A、D1和D3以及细胞周期蛋白依赖性激酶（CDK）4和6的蛋白表达显著降低相关，并伴随p21waf1/Cip1、p27Kip1和p53的诱导。MCF-7细胞暴露于SeC导致凋亡，表现为半胱天冬酶激活、聚（ADP-核糖）聚合酶裂解和DNA片段化。SeC处理还触发了JNK、p38丝裂原活化蛋白激酶（MAPK）、细胞外信号调节激酶（ERK）和Akt的激活。ERK抑制剂（U0126）和Akt抑制剂（LY294002），而非JNK抑制剂（SP600125）和p38 MAPK抑制剂（SB203580），可抑制SeC诱导的MCF-7细胞S期停滞和凋亡。这些发现建立了PI3K/Akt途径、MAPK途径与SeC诱导的MCF-7细胞周期停滞和凋亡之间的机制联系。
