Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells

H. T. Chang, C. S. Liu, C. T. Chou, C. H. Hsieh, C. H. Chang, W. C. Chen, S. I. Liu, S. S. Hsu, J. S. Chen, B. P. Jiann, J. K. Huang, C. R. Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

16 Scopus citations

Abstract

Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblast-like cells is unknown. In human MG63 osteosarcoma cells, the effect of econazole on intracellular Ca2+ concentrations ([Ca2+]i) was explored by using fura-2. At a concentration of 0.1 μM, econazole started to cause a rise in [Ca 2+]i in a concentration-dependent manner. Econazole-induced [Ca2+]i rise was reduced by 74% by removal of extracellular Ca2+. The econazole-induced Ca2+ influx was mediated via a nimodipine-sensitive pathway. In Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca 2+-ATPase, caused a [Ca2+]i rise, after which the increasing effect of econazole on [Ca2+]i was abolished. Pretreatment of cells with econazole to deplete Ca2+ stores totally prevented thapsigargin from releasing Ca2+. U73122, an inhibitor of phospholipase C, abolished histamine (an inositol 1,4,5-trisphosphate-dependent Ca2+ mobilizer)-induced, but not econazole-induced, [Ca2+]i rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca2+ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca 2+]i by stimulating Ca2+ influx and Ca 2+ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca2+ entry.

Original languageEnglish
Pages (from-to)453-458
Number of pages6
JournalHuman and Experimental Toxicology
Volume24
Issue number9
DOIs
StatePublished - 09 2005
Externally publishedYes

Keywords

  • Ca
  • Ca stores
  • Econazole
  • Fura-2
  • Human MG63 osteosarcoma cells

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