Chk1, but not Chk2, is responsible for G2/M phase arrest induced by diallyl disulfide in human gastric cancer BGC823 cells

被引：20

作者：

Bo, Su ^{[1
,2
,3
]}

Hui, He ^{[1
,2
]}

Li, Wang ^{[1
,2
]}

Hui, Ling ^{[1
,2
]}

Hong, Xia ^{[1
,2
]}

Lin, Dong ^{[1
,2
]}

Dai Wen-Xiang ^{[1
]}

Wu You-Hua ^{[1
]}

Ai Xiao-Hong ^{[1
]}

Hao, Jiang ^{[1
]}

Qi, Su ^{[1
,2
]}

机构：

[1] Univ South China, Affiliated Hosp 1, Ctr Gastr Canc Res Hunan Prov, Hengyang 421001, Hunan, Peoples R China

[2] Univ South China, Canc Res Inst, Key Lab Canc Cellular & Mol Pathol Hunan Prov Uni, Hengyang 421001, Hunan, Peoples R China

[3] Univ South China, Inst Pharm & Pharmacol, Key Lab Pharrnacoprote Hunan Prov Univ, Hengyang 421001, Hunan, Peoples R China

来源：

FOOD AND CHEMICAL TOXICOLOGY | 2014年 / 68卷

关键词：

Gastric cancer; Diallyl disulfide; G2/M arrest; Chk1/2; kinase; CYCLE ARREST; G(2)/M ARREST; KINASE; APOPTOSIS; ACTIVATION; CHECKPOINT; EXPRESSION; INVOLVEMENT; MECHANISMS; MUTATIONS;

D O I：

10.1016/j.fct.2014.03.007

中图分类号：

TS2 [食品工业];

学科分类号：

100403 [营养与食品卫生学];

摘要：

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, GADD45 alpha 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. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：61 / 70

页数：10

共 37 条

[1]

Gallic acid causes inactivating phosphorylation of cdc25A/cdc25C-cdc2 via ATM-Chk2 activation, leading to cell cycle arrest, and induces apoptosis in human prostate carcinoma DU145 cells [J].