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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allyl Compounds / pharmacology*
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects*
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CDC2 Protein Kinase
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Carcinoma, Squamous Cell*
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Cell Line, Tumor
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Cell Survival / drug effects
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Cyclin B1 / drug effects
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Cyclin B1 / genetics
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Cyclin-Dependent Kinases / drug effects
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism
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Disulfides / pharmacology*
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Drug Screening Assays, Antitumor
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Esophageal Neoplasms*
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Esophageal Squamous Cell Carcinoma
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G2 Phase Cell Cycle Checkpoints / drug effects*
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Gene Expression Regulation, Neoplastic / drug effects*
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Humans
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MAP Kinase Signaling System / drug effects
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RNA, Messenger / drug effects*
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RNA, Messenger / metabolism
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Signal Transduction / drug effects
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Tumor Suppressor Protein p53 / drug effects
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Tumor Suppressor Protein p53 / metabolism
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cdc25 Phosphatases / drug effects
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cdc25 Phosphatases / genetics
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rho GTP-Binding Proteins / drug effects
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rho GTP-Binding Proteins / metabolism
Substances
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Allyl Compounds
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Antineoplastic Agents
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CCNB1 protein, human
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Cyclin B1
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Disulfides
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RNA, Messenger
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Tumor Suppressor Protein p53
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diallyl disulfide
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CDC2 Protein Kinase
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CDK1 protein, human
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Cyclin-Dependent Kinases
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CDC25C protein, human
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cdc25 Phosphatases
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rho GTP-Binding Proteins