Docetaxel-mediated apoptosis in myeloid progenitor TF-1 cells is mitigated by zinc: Potential implication for prostate cancer therapy

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 r...

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Bibliographic Details
Published in:The Prostate 2011-09, Vol.71 (13), p.1413-1419
Main Authors: Makhov, Peter, Kutikov, Alexander, Golovine, Konstantin, Uzzo, Robert G., Canter, Daniel J., Kolenko, Vladimir M.
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Phytogenic - pharmacology
apoptosis
Apoptosis - drug effects
cancer
docetaxel
Humans
Male
Myeloid Progenitor Cells - drug effects
prostate
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Taxoids - pharmacology
zinc
Zinc - metabolism
Zinc - pharmacology
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Summary: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 pre‐mitotic 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. © 2011 Wiley‐Liss, Inc.
ISSN:0270-4137
1097-0045
DOI:10.1002/pros.21357