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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) 71:1413-1419.
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.
Publication Date: 2011-09-01.
PMCID: PMC3106130
Last updated on Monday, May 04, 2020