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- Title
Econazole induces increases in free intracellular Ca<sup>2+</sup> concentrations in human osteosarcoma cells.
- Authors
Chang, H.-T.; Liu, C.-S.; Chou, C.-T.; Hsieh, C.-H.; Chang, C.-H.; Chen, W.-C.; Liu, S.-I.; Hsu, S.-S.; Chen, J.-S.; Jiann, B.-P.; Huang, J.-K.; Jan, C.-R.
- 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 [Ca2+]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 Ca2+-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 [Ca2+]i by stimulating Ca2+ influx and Ca2+ release from the endoplasmic reticulum via a phospholipase C-independent manner. In contrast, econazole acts as a potent blocker of store-operated Ca2+ entry.
- Subjects
ANTI-infective agents; ANTIFUNGAL agents; TOXICOLOGY; OSTEOSARCOMA; CLINICAL toxicology; MOLECULAR toxicology
- Publication
Human & Experimental Toxicology, 2005, Vol 24, Issue 9, p453
- ISSN
0960-3271
- Publication type
Article
- DOI
10.1191/0960327105ht558oa