Effect of miconazole on intracellular Ca2+ levels and proliferation in human osteosarcoma cells |
| |
Authors: | Chang Hong-Tai Chen Wei-Chung Chen Jin-Shyr Lu Yih-Chau Hsu Shu-Shong Wang Jue-Long Cheng He-Hsiung Cheng Jin-Shiung Jiann Bang-Ping Chiang An-Jen Huang Jong-Khing Jan Chung-Ren |
| |
Affiliation: | Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan 813. |
| |
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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|