title: Diallyl disulfide selectively causes checkpoint kinase-1 mediated G2/M arrest in human MGC803 gastric cancer cell line.
abstract: Previous studies have shown that diallyl disulfide (DADS), a naturally occurring anticancer agent in garlic, arrested human gastric cancer cells (MGC803) in the G2/M phase of the cell cycle. Due to the importance of cell cycle redistribution in DADS-mediated anticarcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. In the present study, the northern blot analysis showed that mRNA expression of for Chkl and Chk2 was unchanged. Notably, DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, activated phospho-ATR (ATM-RAD3-related gene), and dowregulated CDC25C and cyclin B1 expression. Furthermore, CDC25C was immunoprecipitated by anti-Chk1 but not anti-Chk2. Results of the overexpression and knockdown studies, showed that Chk1 but not Chk2 regulated the DADS-induced G2/M arrest of MGC803 cells. The overexpression of Chk1 resulted in significantly increased DADS-induced G2/M arrest, increased DADS-induced Chk1 phosphorylation and inhibited CDC25C expression. Knockdown of Chk1 reduced DADS‑induced G2/M arrest and blocked the DADS-induced inhibition of CDC25C and cyclin B1 expression. These results suggested that Chk1 is important in DADS‑induced cell cycle G2/M arrest in the human MGC803 gastric cancer cell line. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/CDC25C/cyclin B1.
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, Hengyang, Hunan 421001, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, Hengyang, Hunan 421001, P.R. China.
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Lu
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, Hengyang, Hunan 421001, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: He
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, Hengyang, Hunan 421001, P.R. China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Xiao
authors.affiliation: Center for Gastric Cancer Research of Hunan Province, University of South China, Hengyang, Hunan 421001, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Key Laboratory of Tumor Cellular and Molecular Pathology (University of South China), College of Hunan Province, Cancer Research Institute, Hengyang, Hunan 421001, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Su
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2 / Q000235:genetics / Q000378:metabolism*; D004220:Disulfides / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; D004220:Disulfides; C028009:diallyl disulfide; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1