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Effect of thimerosal on Ca 2+ movement and apoptosis in PC3 prostate cancer cells
Author(s) -
Liao WeiChuan,
Chou ChiangTing,
Kuo ChunChi,
Pan ChihChuan,
Kuo DaihHuang,
Shieh Pochuen,
Cheng JinShiung,
Jan ChungRen,
Shaw ChenFu
Publication year - 2011
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.20434
Subject(s) - thimerosal , bapta , endoplasmic reticulum , ionomycin , chemistry , protein kinase c , propidium iodide , apoptosis , phospholipase c , programmed cell death , phorbol , extracellular , kinase , biochemistry , microbiology and biotechnology , intracellular , signal transduction , biology , medicine , dermatology
The present study evaluated the effects of thimerosal, a vaccine preservative, on cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ) in human prostate cancer cells (PC3). Thimerosal (10–200 µM) increased [Ca 2+ ] i in a concentration‐dependent manner. The Ca 2+ signal was reduced partly by removing extracellular Ca 2+ . Thimerosal‐induced Ca 2+ influx was inhibited by econazole, SKF963656, the phospholipase A 2 inhibitor aristolochic acid, and protein kinase C modulators [phorbol 12‐myristate 13‐acetate (PMA) and GF109203X]. In Ca 2+ ‐free medium, a 200‐µM thimerosal‐induced [Ca 2+ ] i rise was partly inhibited after pretreatment with 2,5‐di‐tert‐butylhydroquinone (BHQ) (an endoplasmic reticulum Ca 2+ pump inhibitor). Thimerosal at 1–7 µM induced cell death in a concentration‐dependent manner that was not reversed when cytosolic Ca 2+ was chelated with 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid (BAPTA). Propidium iodide staining suggests that apoptosis played a role in the death. Collectively, in PC3 cells, thimerosal induced [Ca 2+ ] i rise by causing Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via store‐operated Ca 2+ channels in a manner regulated by protein kinase C and phospholipase A2. Thimerosal also induced cell death in a Ca 2+ ‐independent apoptotic manner. Drug Dev Res 72: 330–336, 2011. © 2011 Wiley‐Liss, Inc.