Journal
HUMAN & EXPERIMENTAL TOXICOLOGY
Volume 24, Issue 9, Pages 453-458Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1191/0960327105ht558oa
Keywords
Ca2+; Ca2+ stores; econazole; fura-2; human MG63 osteosarcoma cells
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Econazole is an antifungal drug with different in vitro effects. However, econazole's effect on osteoblastlike 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 mu M, 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 relea-sing Ca2+. U73122, an inhibitor of phospholipase Q abolished histamine (an inositol 1,4,5-trisphosphatedependent Ca2+ mobilizer)-induced, but not econazoleinduced, [Ca2+](i) rise. Econazole inhibited 76% of thapsigargin-induced store-operated Ca2+ entry. These findings suggest that in MG63 osteosarcoma cells, econazole increases [Ca2+](j) 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.
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