Effect of miconazole on intracellular Ca2+ levels and proliferation in human osteosarcoma cells.
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.
Chang
Hong-Tai
HT
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813.
Chen
Wei-Chung
WC
Chen
Jin-Shyr
JS
Lu
Yih-Chau
YC
Hsu
Shu-Shong
SS
Wang
Jue-Long
JL
Cheng
He-Hsiung
HH
Cheng
Jin-Shiung
JS
Jiann
Bang-Ping
BP
Chiang
An-Jen
AJ
Huang
Jong-Khing
JK
Jan
Chung-Ren
CR
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
D002121:Calcium Channel Blockers; D008825:Miconazole; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium