Effect of clotrimazole on cytosolic Ca2+ rise and viability in HA59T human hepatoma cells. (April 2013)

• Record Type: Journal Article
• Authors: Horng, Chi-Ting; Chiang, Ni-Na; Chen, I-Li; Liang, Wei-Zhe; Chen, I-Shu; Kuo, Daih-Huang; Shieh, Po-Chuen; Jan, Chung-Ren
• Is Part Of: Journal of receptor and signal transduction research. Volume 33:Number 2(2013)
• Page Start: 89
• Page End: 95
• Publication Date: 2013-04
• Subjects: Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.3109/10799893.2013.764321
• Languages: English
• ISSNs: 1079-9893

Abstract

<abstract> <title>Abstract</title> <p>Clotrimazole is an antimycotic imidazole derivative that interferes with cellular Ca<sup>2+</sup> homeostasis. This study examined the effect of clotrimazole on cytosolic Ca<sup>2+</sup> concentrations ([Ca<sup>2+</sup>]<italic><sub>i</sub></italic>) and viability in HA59T human hepatoma cells. The Ca<sup>2+</sup>-sensitive fluorescent dye fura-2 was applied to measure [Ca<sup>2+</sup>]<italic><sub>i</sub></italic>. Clotrimazole induced [Ca<sup>2+</sup>]<italic><sub>i</sub></italic> rises in a concentration-dependent manner. The response was reduced by removing extracellular Ca<sup>2+</sup>. Clotrimazole-evoked Ca<sup>2+</sup> entry was suppressed by store-operated channel inhibitors (nifedipine, econazole and SK&F96365) and protein kinase C modulators (GF109203X and phorbol, 12-myristate, 13-acetate). In Ca<sup>2+</sup>-free medium, incubation with the endoplasmic reticulum Ca<sup>2+</sup> pump inhibitor 2, 5-di-tert-butylhydroquinone abolished clotrimazole-induced [Ca<sup>2+</sup>]<italic><sub>i</sub></italic> rise. Inhibition of phospholipase C with U73122 abolished clotrimazole-induced [Ca<sup>2+</sup>]<italic><sub>i</sub></italic> rise. At 10–40 µM, clotrimazole inhibited cell viability, which was not reversed by chelating cytosolic Ca<sup>2+</sup>. Clotrimazole at 10 and 30 µM also induced apoptosis. Collectively, in HA59T cells, clotrimazole-induced [Ca<sup>2+</sup>]<italic><sub>i</sub></italic> rises by evoking phospholipase C-dependent Ca<sup>2+</sup> release from the endoplasmic reticulum and Ca<sup>2+</sup> entry via store-operated Ca<sup>2+</sup> channels. Clotrimazole also caused apoptosis.</p> </abstract>