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Diallyl Trisulfide-Induced G2/M Phase Cell Cycle Arrest in DU145 Cells Is Associated with Delayed Nuclear Translocation of Cyclin-Dependent Kinase 1

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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.

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Authors and Affiliations

  1. Department of Pharmacology & Chemical Biology University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, 15213, USA

    Anna Herman-Antosiewicz, Young-Ae Kim, Su-Hyeong Kim, Dong Xiao & Shivendra V. Singh

  2. Department of Molecular Biology, University of Gdańsk, Gdańsk, Poland

    Anna Herman-Antosiewicz

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  1. Anna Herman-Antosiewicz
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  2. Young-Ae Kim
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  3. Su-Hyeong Kim
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  4. Dong Xiao
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  5. Shivendra V. Singh
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Corresponding author

Correspondence to Shivendra V. Singh.

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Grant support

This investigation was supported by the USPHS grant RO1 CA113363–05 (to S.V.S.) awarded by the National Cancer Institute.

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Herman-Antosiewicz, A., Kim, YA., Kim, SH. et al. Diallyl Trisulfide-Induced G2/M Phase Cell Cycle Arrest in DU145 Cells Is Associated with Delayed Nuclear Translocation of Cyclin-Dependent Kinase 1. Pharm Res 27, 1072–1079 (2010). https://doi.org/10.1007/s11095-010-0060-7

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  • DOI: https://doi.org/10.1007/s11095-010-0060-7

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