title: Econazole induces increases in free intracellular Ca2+ concentrations in human osteosarcoma cells.
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 microM, 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 Ca+ -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.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
authors.forename: H T
authors.initials: HT
authors.lastname: Chang
authors.forename: C S
authors.initials: CS
authors.lastname: Liu
authors.forename: C T
authors.initials: CT
authors.lastname: Chou
authors.forename: C H
authors.initials: CH
authors.lastname: Hsieh
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
authors.forename: W C
authors.initials: WC
authors.lastname: Chen
authors.forename: S I
authors.initials: SI
authors.lastname: Liu
authors.forename: S S
authors.initials: SS
authors.lastname: Hsu
authors.forename: J S
authors.initials: JS
authors.lastname: Chen
authors.forename: B P
authors.initials: BP
authors.lastname: Jiann
authors.forename: J K
authors.initials: JK
authors.lastname: Huang
authors.forename: C R
authors.initials: CR
authors.lastname: Jan
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004464:Econazole / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D009553:Nimodipine / Q000494:pharmacology; D012516:Osteosarcoma; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000935:Antifungal Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D009553:Nimodipine; D019284:Thapsigargin; D004464:Econazole; D002118:Calcium