Zinc deficiency reduces paclitaxel efficacy in LNCaP prostate cancer cells

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Alison N. Killileab, H. Downingb and W. Killileaa, ,

aNutrition & Metabolism Center, Children’s Hospital Oakland Research

Institute, 5700 Luther King Jr. Way, Oakland, CA 94609-1673, USA

bLife Sciences Division, Lawrence Berkeley National Laboratory, Berkeley,

CA, USA

Received 11 July 2007;  revised 20 August 2007;  accepted 21 August 2007. 

Available online 1 October 2007.

Abstract

Chemotherapeutics used to treat prostate cancer are often from a class of

drugs that target microtubule networks, such as paclitaxel. A previous

report indicated that supplemental zinc sensitized prostate cancer cells to

paclitaxel-induced apoptosis, suggesting that increased zinc levels might

enhance paclitaxel efficacy. The effect of zinc deficiency on paclitaxel

activity is not known though, so we tested this in two prostate cancer cell

lines maintained under moderately zinc-deficient conditions. LNCaP and PC3

cell lines were used as models of early and late-stage prostate cancer,

respectively. Cells cultured in reduced zinc levels did not demonstrate

altered cell viability, growth rates, or intracellular zinc content.

Additionally, zinc deficiency alone had no apparent effect on cell cycle

kinetics or apoptosis levels. However, the IC50 for paclitaxel-induced cell

cycle arrest increased in LNCaP cells from zinc-deficient compared to

zinc-replete conditions. Consequently, paclitaxel-induced apoptosis was

reduced in LNCaP cells from zinc-deficient compared to zinc-replete

conditions. In PC3 cells, the effects of paclitaxel were independent of zinc

status. Reduced extracellular zinc levels were shown to affect paclitaxel

activity in a prostate cancer cell line. Given the prevalence of zinc

deficiency, determining how chemotherapeutic action is modulated by zinc

adequacy may have clinical importance.