title: Chk1, but not Chk2, is responsible for G2/M phase arrest induced by diallyl disulfide in human gastric cancer BGC823 cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Su
authors.initials: S
authors.lastname: Bo
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Hui
authors.affiliation: 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.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Ling
authors.initials: L
authors.lastname: Hui
authors.affiliation: 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.
authors.forename: Xia
authors.initials: X
authors.lastname: Hong
authors.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Wen-Xiang
authors.initials: WX
authors.lastname: Dai
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
authors.forename: You-Hua
authors.initials: YH
authors.lastname: Wu
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Ai
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China. Electronic address: jhao16859@163.com.
authors.forename: Jiang
authors.initials: J
authors.lastname: Hao
authors.affiliation: 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. Electronic address: suqi1945@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Qi
mesh_terms: D000498:Allyl Compounds / Q000009:adverse effects*; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D056744:Cyclin B1 / Q000235:genetics / Q000378:metabolism; D004220:Disulfides / Q000009:adverse effects*; D015536:Down-Regulation; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; C534699:CCNB1 protein, human; D056744:Cyclin B1; D004220:Disulfides; D034741:RNA, Small Interfering; C028009:diallyl disulfide; D011494:Protein Kinases; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases
keywords: Chk1/2 kinase; Diallyl disulfide; G2/M arrest; Gastric cancer