Bo Su, Hui He, Li Wang, Hui Ling, Hong Xia, Lin Dong, Dai Wen-Xiang, Wu You-Hua, Ai Xiao-Hong, Hao Jiang, Qi Su
Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China; Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, China; Key Laboratory for Pharmacoproteomics of Hunan Provincial University, Institute of Pharmacy and Pharmacology, University of South China, Hengyang, Hunan 421001, China.
Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China; Key Laboratory of Cancer Cellular and Molecular Pathology of Hunan Provincial University, Cancer Research Institute, University of South China, Hengyang, Hunan 421001, China.
Food Chem Toxicol. 2014 Jun;68:61-70. doi: 10.1016/j.fct.2014.03.007. Epub 2014 Mar 18.
Diallyl disulfide (DADS) has been shown to cause G2/M phase cell cycle arrest in several human cancers. Here we demonstrate a mechanism by which DADS induces G2/M phase arrest in BGC823 human gastric cancer cells via Chk1. From cell cycle gene array results, we next confirmed that cyclin B1 expression was decreased by DADS, while the expression of p21, GADD45α and p53 were increased. Despite the lack of change in Chk1 gene expression in response to DADS according to the array analysis, intriguingly overexpression of Chk1, but not Chk2, exhibited increased accumulation in G2/M phase. Moreover, overexpression of Chk1 promoted the effect of DADS-induced G2/M arrest. Augmented phosphorylation of Chk1 by DADS was observed in Chk1-transfected cells, followed by downregulation of Cdc25C and cyclin B1 proteins. In contrast, phosphorylated Chk2 showed no obvious change in Chk2-transfected cells after DADS treatment. Furthermore, knockdown of Chk1 by siRNA partially abrogated DADS-induced downregulation of Cdc25C and cyclin B1 proteins and G2/M arrest. In contrast, knockdown of Chk2 did not show these effects. Therefore, these data indicate that DADS may specifically modulate Chk1 phosphorylation, and DADS-induced G2/M phase arrest in BGC823 cells could result in part from Chk1-mediated inhibition of the Cdc25C/cyclin B1 pathway.
二烯丙基二硫化物（DADS）已被证明可导致多种人类癌症发生G2/M期细胞周期阻滞。在此我们阐述了一种机制，即DADS通过Chk1诱导BGC823人胃癌细胞发生G2/M期阻滞。根据细胞周期基因芯片结果，我们接下来证实DADS可降低细胞周期蛋白B1的表达，同时增加p21、GADD45α和p53的表达。尽管根据芯片分析，Chk1基因表达在DADS作用下没有变化，但有趣的是，Chk1而非Chk2的过表达显示在G2/M期的积累增加。此外，Chk1的过表达增强了DADS诱导的G2/M期阻滞作用。在Chk1转染细胞中观察到DADS增强了Chk1的磷酸化，随后Cdc25C和细胞周期蛋白B1蛋白下调。相反，DADS处理后，Chk2转染细胞中磷酸化的Chk2没有明显变化。此外，用小干扰RNA（siRNA）敲低Chk1可部分消除DADS诱导的Cdc25C和细胞周期蛋白B1蛋白下调以及G2/M期阻滞。相反，敲低Chk2没有显示出这些作用。因此，这些数据表明DADS可能特异性调节Chk1磷酸化，并且DADS诱导的BGC823细胞G2/M期阻滞可能部分是由于Chk1介导的对Cdc25C/细胞周期蛋白B1途径的抑制。
