title: Effect of miconazole on intracellular Ca2+ levels and proliferation in human osteosarcoma cells.
abstract: The effect of miconazole, an anti-fungal drug, on cytoplasmic free Ca2+ concentrations ([Ca2+]i) in human osteosarcoma cells (MG63) was explored by using the Ca2+-sensitive dye fura-2. Miconazole acted in a concentration-dependent manner with an EC50 of 75 microM. The Ca2+ signal comprised a gradual rise and a sustained elevation. Removal of extracellular Ca2+ reduced 50% of the signal. In Ca2+-free medium, the [Ca2+]i rise induced by 1 microM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) was completely inhibited by pretreatment with 20 microM miconazole. Pretreatment with thapsigargin partly inhibited miconazole-induced Ca2+ release. The miconazole-induced Ca2+ release was not changed by inhibition of phospholipase C with 2 microM U73122. By using tetrazolium as a fluorescent probe, it was shown that 10-100 microM miconazole decreased cell proliferation rate in a concentration-dependent manner. Collectively, this study shows that miconazole induces [Ca2+]i rises in human osteosarcoma cells via releasing Ca2+ mainly from the endoplasmic reticulum in a manner independent of phospholipase C activity, and by causing Ca2+ influx. Furthermore, miconazole may be cytotoxic to the cells at higher concentrations.
authors.affiliation: Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.
authors.forename: Hong-Tai
authors.initials: HT
authors.lastname: Chang
authors.forename: Wei-Chung
authors.initials: WC
authors.lastname: Chen
authors.forename: Jin-Shyr
authors.initials: JS
authors.lastname: Chen
authors.forename: Yih-Chau
authors.initials: YC
authors.lastname: Lu
authors.forename: Shu-Shong
authors.initials: SS
authors.lastname: Hsu
authors.forename: Jue-Long
authors.initials: JL
authors.lastname: Wang
authors.forename: He-Hsiung
authors.initials: HH
authors.lastname: Cheng
authors.forename: Jin-Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Bang-Ping
authors.initials: BP
authors.lastname: Jiann
authors.forename: An-Jen
authors.initials: AJ
authors.lastname: Chiang
authors.forename: Jong-Khing
authors.initials: JK
authors.lastname: Huang
authors.forename: Chung-Ren
authors.initials: CR
authors.lastname: Jan
mesh_terms: D001859:Bone Neoplasms; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D049109:Cell Proliferation; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D008825:Miconazole / Q000494:pharmacology* / Q000633:toxicity; D010006:Osteoblasts / Q000187:drug effects*; D012516:Osteosarcoma; D014407:Tumor Cells, Cultured
chemical_list: D002121:Calcium Channel Blockers; D008825:Miconazole; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium