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Econazole‐induced Ca 2+ fluxes and apoptosis in human oral cancer cells
Author(s) -
Kuo DaihHuang,
Liu LiMin,
Chen HsinWei,
Chen FuAn,
Jan ChungRen
Publication year - 2010
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20366
Subject(s) - econazole , thapsigargin , phospholipase c , endoplasmic reticulum , propidium iodide , fura 2 , microbiology and biotechnology , apoptosis , biology , chemistry , cytosol , biochemistry , pharmacology , programmed cell death , signal transduction , miconazole , enzyme , antifungal
The effect of econazole on cytosolic free Ca 2+ concentrations ([Ca 2+ ] 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 >1 µM increased [Ca 2+ ] i in a concentration‐dependent manner. The Ca 2+ signal was reduced partly by removing extracellular Ca 2+ . The econazole‐induced Ca 2+ influx was sensitive to blockade of aristolochic acid (phospholipase A 2 inhibitor) and GF109203X (PKC inhibitor). In Ca 2+ ‐free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor), 30 µM econazole failed to induce a [Ca 2+ ] i rise. Inhibition of phospholipase C with 2 µM U73122 substantially suppressed econazole‐induced [Ca 2+ ] i rise. At concentrations of 5–70 µM econazole killed cells in a concentration‐dependent manner. The cytotoxic effect of 50 µM econazole was enhanced by prechelating cytosolic Ca 2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). The ERK MAPK inhibitor, PD98059 (10 µM), also enhanced 20 µM econazole‐induced cell death. Propidium iodide staining data suggest that econazole induced apoptosis between concentrations of 10–70 µM. Collectively, in OC2 cells, econazole induced [Ca 2+ ] i rises by causing Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx from phospholipase A 2 /PKC‐regulated Ca 2+ channels. Furthermore, econazole caused cell death appeared to be regulated by ERK MAPK. Drug Dev Res 71: 240–248, 2010. © 2010 Wiley‐Liss, Inc.