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.
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 DU145humanprostate 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: Ann W Hsing; Anand P Chokkalingam; Yu-Tang Gao; M Patricia Madigan; Jie Deng; Gloria Gridley; Joseph F Fraumeni Journal: J Natl Cancer Inst Date: 2002-11-06 Impact factor: 13.506
Authors: Dong Xiao; Sanjay K Srivastava; Karen L Lew; Yan Zeng; Pamela Hershberger; Candace S Johnson; Donald L Trump; Shivendra V Singh Journal: Carcinogenesis Date: 2003-05 Impact factor: 4.944
Authors: Dong Xiao; Sunga Choi; Daniel E Johnson; Victor G Vogel; Candace S Johnson; Donald L Trump; Yong J Lee; Shivendra V Singh Journal: Oncogene Date: 2004-07-22 Impact factor: 9.867
Authors: Clement G Yedjou; Ariane T Mbemi; Felicite Noubissi; Solange S Tchounwou; Nole Tsabang; Marinelle Payton; Lucio Miele; Paul B Tchounwou Journal: Nutrients Date: 2019-02-04 Impact factor: 5.717