The mechanism of bifonazole-induced [Ca2+]i rises and non-Ca2+-triggered cell death in PC3 human prostate cancer cells. (December 2014)

• Record Type: Journal Article
• Authors: Cheng, Jin Shiung; Chou, Chiang-Ting; Liang, Wei-Zhe; Kuo, Chun-Chi; Shieh, Pochuen; Kuo, Daih-Huang; Jan, Chung-Ren
• Is Part Of: Journal of receptor and signal transduction research. Volume 34:Number 6(2014)
• Page Start: 493
• Page End: 499
• Publication Date: 2014-12
• Subjects: Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.3109/10799893.2014.921201
• Languages: English
• ISSNs: 1079-9893

Abstract

<abstract> <title>Abstract</title> <p>Bifonazole is an antifungal drug widely used for treating skin diseases. The effect of bifonazole on physiology of cancer cells is unclear. The effect of bifonazole on cytosolic free Ca<sup>2+</sup> concentrations ([Ca<sup>2+</sup>]<sub>i</sub>) and viability in PC3 human prostate cancer cells was explored. The Ca<sup>2+</sup>-sensitive fluorescent dye, fura-2, was applied to measure [Ca<sup>2+</sup>]<sub>i</sub>. Bifonazole at concentrations of 5–30 µM induced a [Ca<sup>2+</sup>]<sub>i</sub> rise in a concentration-dependent manner. The response was reduced by 50% by removing extracellular Ca<sup>2+</sup>. Bifonazole-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise was not altered by nifedipine, econazole, SK&F96365 and protein kinase C activator, but was inhibited by 75% by GF109203X, a protein kinase C inhibitor. In Ca<sup>2+</sup>-free medium, treatment with the endoplasmic reticulum Ca<sup>2+</sup> pump inhibitor 2, 5-di-tert-butylhydroquinone (BHQ) nearly abolished bifonazole-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise. Conversely, treatment with bifonazole abolished BHQ-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise. Inhibition of phospholipase C with U73122 abolished bifonazole-induced [Ca<sup>2+</sup>]<sub>i</sub> rise. At 30–100 µM, bifonazole decreased cell viability concentration-dependently, which was not reversed by chelating cytosolic Ca<sup>2+</sup> with 1, 2-bis(2-aminophenoxy)ethane-N, N, N″, N′-tetraacetic acid/acetoxy methyl. Annexin V/propidium iodide staining data suggest that bifonazole (30–100 µM) induced apoptosis concentration-dependently. Together, in PC3 human prostate cancer cells, bifonazole induced [Ca<sup>2+</sup>]<sub>i</sub> rises by inducing phospholipase C- and protein kinase C-dependent Ca<sup>2+</sup> release from the endoplasmic reticulum and Ca<sup>2+</sup> influx <italic>via</italic> non-store-operated pathways. Bifonazole induced cell death that might involve apoptosis.</p> </abstract>