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Makhov P , Kutikov A , Golovine K , Uzzo RG , Canter DJ , Kolenko VM
Docetaxel-Mediated Apoptosis in Myeloid Progenitor TF-I Cells Is Mitigated by Zinc: Potential Implication for Prostate Cancer Therapy
Prostate. 2011 Sep;71(13) :1413-1419
PMID: WOS:000294443700006    PMCID: PMC3106130   
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BACKGROUND. Docetaxel-based combination chemotherapy is approved by the FDA for the treatment of metastatic castration-resistant prostate cancer. Unfortunately, docetaxel's efficacy is significantly limited by its considerable toxicity on hematopoietic progenitor cells, thus necessitating dose reduction or even discontinuation of the chemotherapy. Induction of premitotic arrest protects cells against docetaxel-mediated toxicity and affords therapeutic opportunities. METHODS. Cell cycle progression was examined by propidium iodide staining. Zinc uptake was determined by FluoZin-3 AM staining. Apoptotic DNA fragmentation was detected using APO-BRDU kit. RESULTS. In the course of our current work, we treated the myeloid progenitor TF-1 cells and the castration-resistant PC-3 and DU-145 prostate cancer cells with physiologically relevant concentrations of zinc. In doing so, we were able to prevent docetaxel-mediated mitotic arrest in zinc accumulating myeloid progenitor TF-1 cells but not in castration-resistant PC-3 and DU-145 prostate cancer cells. Moreover, pre-treatment with zinc abolished docetaxel-induced apoptosis in TF-1 cells, whereas such treatment had no effect on apoptosis in PC-3 and DU-145 prostate cancer cells. CONCLUSIONS. Our results suggest that zinc can protect myeloid progenitor cells against docetaxel-induced toxicity without compromising the drug's anti-tumor activity. Prostate 71: 1413-1419, 2011. (C) 2011 Wiley-Liss, Inc.
Makhov, Peter Kutikov, Alexander Golovine, Konstantin Uzzo, Robert G. Canter, Daniel J. Kolenko, Vladimir M. National Institutes of Health[P30 CA006927, RO1 CA108890, RO1 CA134463]; American Institute for Cancer Research; Department of Defense Grant sponsor: National Institutes of Health P30 CA006927 RO1 CA108890 RO1 CA134463; Grant sponsor: American Institute for Cancer Research; Grant sponsor: Department of Defense, Physician Research Training Award. 33 Wiley-blackwell Malden 814jc