Diallyl trisulfide-induced G2/M phase cell cycle arrest in DU145 cells is associated with delayed nuclear translocation of cyclin-dependent kinase 1.

Abstract

PURPOSE:

The present study was undertaken to gain insight into the molecular mechanism of G2/M phase cell cycle arrest resulting from treatment of DU145 cells with diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic.

METHODS:

Cell cycle distribution was determined by flow cytometry. Immunoblotting was performed to determine protein expression. Overexpression of wild-type or mutant Cdc25C was achieved by transient transfection. Nuclear and cytoplasmic localization of cyclin B1 and cyclin-dependent kinase 1 (cdk1) was studied by immunoblotting.

RESULTS:

Exposure of DU145 human prostate cancer cells to DATS resulted in concentration- and time-dependent accumulation of G2/M phase cells, which correlated with down-regulation as well as increased S216 phosphorylation of Cdc25C. Ectopic expression of wild-type or redox-insensitive mutants (C330S and C330S/C377S) or S216A mutant of Cdc25C failed to confer protection against DATS-induced G2/M phase arrest. The DATS-mediated G2/M phase cell cycle arrest was also independent of reduced complex formation between cdk1 and cyclin B1, but correlated with delayed nuclear translocation of cdk1.

CONCLUSION:

The present study indicates that the DATS-mediated G2/M phase cell cycle arrest in DU145 cells results from differential kinetics of nuclear localization of cdk1 and cyclin B1.

• Authors: Anna Herman-Antosiewicz, Young-Ae Kim, Su-Hyeong Kim, Dong Xiao, Shivendra V Singh
• Journal: Pharmaceutical research (Pharm Res) Vol. 27 Issue 6 Pg. 1072-9 (Jun 2010) ISSN: 1573-904X [Electronic] United States
• PMID: 20143254 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Allyl Compounds
• Antineoplastic Agents, Phytogenic
• Cyclin B1
• Sulfides
• diallyl trisulfide
• CDC2 Protein Kinase
• CDC25C protein, human
• cdc25 Phosphatases

Topics

• Allyl Compounds (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• CDC2 Protein Kinase (metabolism)
• Cell Division (drug effects)
• Cell Line, Tumor
• Cell Nucleus (drug effects, metabolism)
• Cyclin B1 (metabolism)
• G2 Phase (drug effects)
• Garlic (chemistry)
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Prostatic Neoplasms (enzymology, prevention & control)
• Protein Transport (drug effects)
• Sulfides (pharmacology, therapeutic use)
• cdc25 Phosphatases (genetics, metabolism)