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


CONCLUSIONS
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.
Department of Pharmacology & Chemical Biology University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213, USA. wuzel@biotech.ug.gda.pl
Anna
A
Herman-Antosiewicz
Young-Ae
YA
Kim
Su-Hyeong
SH
Kim
Dong
D
Xiao
Shivendra V
SV
Singh
D000498:Allyl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects*; D005737:Garlic / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D021381:Protein Transport / Q000187:drug effects; D013440:Sulfides / Q000494:pharmacology* / Q000627:therapeutic use; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism
D000498:Allyl Compounds; D000972:Antineoplastic Agents, Phytogenic; D056744:Cyclin B1; D013440:Sulfides; C042577:diallyl trisulfide; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases