Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma

Oncol Rep. 2014 Oct;32(4):1748-56. doi: 10.3892/or.2014.3361. Epub 2014 Jul 25.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • CDC2 Protein Kinase
  • Carcinoma, Squamous Cell*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclin B1 / drug effects
  • Cyclin B1 / genetics
  • Cyclin-Dependent Kinases / drug effects
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Disulfides / pharmacology*
  • Drug Screening Assays, Antitumor
  • Esophageal Neoplasms*
  • Esophageal Squamous Cell Carcinoma
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • RNA, Messenger / drug effects*
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Tumor Suppressor Protein p53 / drug effects
  • Tumor Suppressor Protein p53 / metabolism
  • cdc25 Phosphatases / drug effects
  • cdc25 Phosphatases / genetics
  • rho GTP-Binding Proteins / drug effects
  • rho GTP-Binding Proteins / metabolism

Substances

  • Allyl Compounds
  • Antineoplastic Agents
  • CCNB1 protein, human
  • Cyclin B1
  • Disulfides
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • diallyl disulfide
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases
  • CDC25C protein, human
  • cdc25 Phosphatases
  • rho GTP-Binding Proteins