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Makhov P , Kutikov A , Golovine K , Uzzo RG , Canter DJ , Kolenko VM
Docetaxel-mediated apoptosis in myeloid progenitor TF-1 cells is mitigated by zinc: potential implication for prostate cancer therapy
Prostate. 2011 Sep 15;71(13) :1413-9
PMID: 21308721    PMCID: PMC3106130    URL: https://www.ncbi.nlm.nih.gov/pubmed/21308721
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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 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.
Makhov, Peter Kutikov, Alexander Golovine, Konstantin Uzzo, Robert G Canter, Daniel J Kolenko, Vladimir M eng R01CA134463/CA/NCI NIH HHS/ R01 CA134463/CA/NCI NIH HHS/ R01 CA134463-02/CA/NCI NIH HHS/ P30 CA006927/CA/NCI NIH HHS/ R01CA108890/CA/NCI NIH HHS/ R01 CA108890/CA/NCI NIH HHS/ R01 CA108890-04/CA/NCI NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Prostate. 2011 Sep 15;71(13):1413-9. doi: 10.1002/pros.21357. Epub 2011 Feb 9.