title: Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with high incidence and mortality worldwide. Diallyl disulfide (DADS) is a natural organosulfur compound, isolated from garlic. In this study, MTT assay showed that DADS significantly reduced cell viability in a dose- and time-dependent manner in ESCC cells, with lower toxicity in normal liver cells. Cell cycle analysis revealed that DADS made G2/M phase arrest. Molecular analysis suggested that this cell cycle arrest was likely made by the decrease of cyclin B1, cdc2, p-cdc2, cdc25c in concomitance with activation of the p53/p21 pathway. Apoptosis was detected by Annexin V/PI staining. The molecule markers showed that DADS induced apoptosis through activating caspases, altering the Bax/Bcl-2 balance and suppressing the MEK-ERK pathway. Our data indicated that DADS has the potential to be an effective and safe anticancer agent for ESCC therapy in the near future.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Digestion, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Feng
authors.affiliation: Department of Digestion, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Digestion, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xijing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Shuqun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Zongfang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Xinlian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Ma
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase; D002294:Carcinoma, Squamous Cell; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056744:Cyclin B1 / Q000187:drug effects / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms; D000077277:Esophageal Squamous Cell Carcinoma; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000378:metabolism; D020687:cdc25 Phosphatases / Q000187:drug effects / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D056744:Cyclin B1; D004220:Disulfides; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C028009:diallyl disulfide; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D020741:rho GTP-Binding Proteins