Abstract
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.