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

Fox Chase Cancer Center, Philadelphia, Pennsylvania.

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.

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.

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.

Our results suggest that zinc can protect myeloid progenitor cells against docetaxel-induced toxicity without compromising the drug's anti-tumor activity.

Written by:
Makhov P, Kutikov A, Golovine K, Uzzo RG, Canter DJ, Kolenko VM.   Are you the author?

Reference: Prostate. 2011 Feb 9. Epub ahead of print.
doi: 10.1002/pros.21357

PubMed Abstract
PMID: 21308721 Prostate Cancer Section