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: Xiaoran Yin, Rong Zhang, Cheng Feng, Jun Zhang, Dong Liu, Kun Xu, Xijing Wang, Shuqun Zhang, Zongfang Li, Xinlian Liu, Hongbing Ma
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 4 Pg. 1748-56 (Oct 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 25175641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, genetics)
• Cyclin-Dependent Kinases (drug effects, genetics, 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, metabolism)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (drug effects, metabolism)
• cdc25 Phosphatases (drug effects, genetics)
• rho GTP-Binding Proteins (drug effects, metabolism)