Effect of clotrimazole on cytosolic Ca(2+) rise and viability in HA59T human hepatoma cells
| Autor: | Pochuen Shieh, Daih-Huang Kuo, Chung-Ren Jan, I-Shu Chen, Ni-Na Chiang, Chi-Ting Horng, I-Li Chen, Wei-Zhe Liang |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Carcinoma
Hepatocellular Nifedipine Cell Survival Apoptosis Biology Pharmacology Biochemistry chemistry.chemical_compound Cytosol Cell Line Tumor Extracellular medicine Imidazole Humans Viability assay Calcium Signaling Clotrimazole Molecular Biology Protein kinase C Protein Kinase C Phospholipase C Endoplasmic reticulum Liver Neoplasms Cell Biology Molecular biology chemistry Type C Phospholipases Phorbol Calcium Fura-2 medicine.drug Signal Transduction |
| Zdroj: | Journal of receptor and signal transduction research. 33(2) |
| ISSN: | 1532-4281 |
| Popis: | Clotrimazole is an antimycotic imidazole derivative that interferes with cellular Ca(2+) homeostasis. This study examined the effect of clotrimazole on cytosolic Ca(2+) concentrations ([Ca(2+)](i)) and viability in HA59T human hepatoma cells. The Ca(2+)-sensitive fluorescent dye fura-2 was applied to measure [Ca(2+)](i). Clotrimazole induced [Ca(2+)](i) rises in a concentration-dependent manner. The response was reduced by removing extracellular Ca(2+). Clotrimazole-evoked Ca(2+) entry was suppressed by store-operated channel inhibitors (nifedipine, econazole and SKF96365) and protein kinase C modulators (GF109203X and phorbol, 12-myristate, 13-acetate). In Ca(2+)-free medium, incubation with the endoplasmic reticulum Ca(2+) pump inhibitor 2,5-di-tert-butylhydroquinone abolished clotrimazole-induced [Ca(2+)](i) rise. Inhibition of phospholipase C with U73122 abolished clotrimazole-induced [Ca(2+)](i) rise. At 10-40 µM, clotrimazole inhibited cell viability, which was not reversed by chelating cytosolic Ca(2+). Clotrimazole at 10 and 30 µM also induced apoptosis. Collectively, in HA59T cells, clotrimazole-induced [Ca(2+)](i) rises by evoking phospholipase C-dependent Ca(2+) release from the endoplasmic reticulum and Ca(2+) entry via store-operated Ca(2+) channels. Clotrimazole also caused apoptosis. |
| Databáze: | OpenAIRE |
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