Zinc Deficiency and Microtubule Function in Prostate Cells
Final rept. 15 Nov 2004-14 Mar 2006
CHILDREN'S HOSPITAL OAKLAND RESEARCH INST OAKLAND CA
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Zinc deficiency is surprisingly common in the US. One organ expected to suffer during zinc deficiency is the prostate, since it is the greatest tissue accumulator of zinc in men. Zinc uptake in prostate epithelial cells is higher than most other cells types in the body, but zinc levels in these cells rapidly decrease upon transformation to a cancerous phenotype. Zinc homeostasis may play important regulatory roles in both normal growth and carcinogenesis within the prostate, however the mechanism remains obscured. The cytoskeleton is a known target of zinc binding in the cell, especially in microtubules. Crystallization studies have defined binding sites for zinc in microtubules, but cellular evidence is lacking. However, it has been proposed that microtubule dynamics may be disrupted when cellular zinc levels drop. Current drugs approved for use or in clinical trials to treat prostate cancer paclitaxel, docetaxel, and 2-methoxyestradiol target the microtubule network resulting in cell death. It is unknown if zinc deficient individuals have alterations in the microtubule network such that the activity of these chemotherapeutic agents is altered. Therefore, we tested the hypothesis that inadequate amounts of zinc disrupts microtubule function and decreases efficacy of microtubule-targeting chemotherapeutic agents in prostate cancer cells.
- Medicine and Medical Research