کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2555053 | 1125027 | 2005 | 11 صفحه PDF | دانلود رایگان |
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 μM. 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 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) was completely inhibited by pretreatment with 20 μM 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 μM U73122. By using tetrazolium as a fluorescent probe, it was shown that 10–100 μM 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.
Journal: Life Sciences - Volume 76, Issue 18, 18 March 2005, Pages 2091–2101