In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 32, No. 9 ( 2005-09), p. 735-741
Abstract:
1. Econazole is used clinically as an antifungal drug with many different in vitro effects. However, the effects of econazole on prostate cancer cells are unknown. The effects of econazole on intracellular Ca 2+ concentrations ([Ca 2+ ] i ) in and the proliferation of human PC3 prostate cancer cells was explored in the present study using fura‐2 and tetrazolium as fluorescent dyes. 2. At a concentration of 0.1 µmol/L, econazole started to increase [Ca 2+ ] i in a concentration‐dependent manner. The econazole‐induced increase in [Ca 2+ ] i was reduced by 48% by removal of extracellular Ca 2+ , suggesting that the econazole‐induced increase in [Ca 2+ ] i was composed of extracellular Ca 2+ influx and intracellular Ca 2+ . 3. This econazole‐induced Ca 2+ influx was via an L‐type Ca 2+ channel‐like pathway. In Ca 2+ ‐free medium, 1 µmol/L thapsigargin, an inhibitor of the endoplasmic reticulum Ca 2+ ‐ATPase, caused a monophasic increase in [Ca 2+ ] i , after which the effect of econazole to increase [Ca 2+ ] i was substantially inhibited. Conversely, pretreatment with 5 µmol/L econazole to deplete intracellular Ca 2+ stores totally prevented thapsigargin from releasing more Ca 2+ . 4. The phospholipase C (PLC) inhibitor U73122 (2 µmol/L) abolished the increase in [Ca 2+ ] i induced by 10 µmol/L ATP (a Ca 2+ mobilizer that needs inositol 1,4,5‐trisphosphate). 5. Overnight incubation with 1–30 µmol/L econazole inhibited proliferation of PC3 cells in a concentration‐dependent manner. 6. These findings suggest that, in PC3 cells, econazole increases [Ca 2+ ] i by stimulating Ca 2+ influx into cells and Ca 2+ release from the endoplasmic reticulum via a PLC‐independent mechanism. Econazole is cytotoxic at submicromolar concentrations.
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/cep.2005.32.issue-9
DOI:
10.1111/j.1440-1681.2005.04254.x
Language:
English
Publisher:
Wiley
Publication Date:
2005
detail.hit.zdb_id:
2020033-X
SSG:
15,3
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