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Maprotiline‐induced Ca 2+ fluxes and apoptosis in human osteosarcoma cells
Author(s) -
Liao WeiChuan,
Huang ChorngChih,
Lu YihChau,
Chi ChaoChuan,
Chu SauTung,
Su HsingHao,
Kuo ChunChi,
Cheng JinShiung,
Tseng LiLing,
Ho ChinMan,
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.20371
Subject(s) - maprotiline , chemistry , bapta , propidium iodide , endoplasmic reticulum , phospholipase a2 , thapsigargin , apoptosis , fura 2 , biochemistry , extracellular , microbiology and biotechnology , endocrinology , cytosol , programmed cell death , biology , enzyme , antidepressant , hippocampus
The effect of maprotiline on cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ) and cell viability was explored in human osteosarcoma cells (MG63), using the fluorescent dyes fura‐2 and WST‐1, respectively. Maprotiline at concentrations of ≥20 µM increased [Ca 2+ ] i in a concentration‐dependent manner. The Ca2+ signal was reduced partly by removing extracellular Ca 2+ . The maprotiline‐induced Ca 2+ influx was sensitive to inhibition by aristolochic acid (a phospholipase A 2 inhibitor). In Ca 2+ ‐free medium, after treatment with 1 µM thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor), 200 µM maprotiline failed to induce a [Ca 2+ ] i rise. At concentrations of 50–100 µM maprotiline killed cells in a concentration‐dependent manner. The cytotoxic effect of 60 µM maprotiline was slightly enhanced by prechelating cytosolic Ca 2+ with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). Propidium iodide staining data suggested that maprotiline induced apoptosis between concentrations of 60–70 µM, which was enhanced by BAPTA. Collectively, in MG63 cells, maprotiline induced [Ca 2+ ] i rises by causing Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx from phospholipase A 2 ‐regulated Ca 2+ channels. Furthermore, maprotiline caused apoptosis that was regulated by Ca 2+ . Drug Dev Res 71: 268–274, 2010. © 2010 Wiley‐Liss, Inc.