Econazole-Induced Ca2+ Fluxes and Apoptosis in Human Oral Cancer Cells

• Main Authors: Li-Min Liu, 劉立敏
• Other Authors: Daih-Huang Kuo
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/43870494502929725430

碩士 === 大仁科技大學 === 製藥科技研究所 === 97 === The effect of econazole on cytosolic free Ca2+ concentrations ([Ca2+]i) and viability was explored in human oral cancer cells (OC2), using the fluorescent dyes fura-2 and WST-1, respectively. Econazole at concentrations of and above 1 M increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca2+. The econazole-induced Ca2+ influx was sensitive to blockade of aristolochic acid (a phospholipase A2 inhibitor) and GF109203X (a protein kinase C inhibitor). In Ca2+-free medium, after treatment with 1 M thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor), 30 M econazole failed to induce a [Ca2+]i rise. Inhibition of phospholipase C with 2 M U73122 substantially suppressed econazole-induced [Ca2+]i rise. At concentrations between 5 and 70 M econazole killed cells in a concentration-dependent manner. The cytotoxic effect of 50 M econazole was not enhanced by prechelating cytosolic Ca2+ with BAPTA/AM. The ERK/MAPK inhibitor PD98059 (10 M) also enhanced 20 M econazole-induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10-70 M. Collectively, in OC2 cells, econazole induced [Ca2+]i rises by causing Ca2+ release from the endoplasmic reticulum and Ca2+ influx from phospholipase A2/protein kinase C-regulated Ca2+ channels. Furthermore, econazole caused apoptosis that was regulated by Ca2+ and ERK/MAPK.