Effect of the organotin compound triethyltin on Ca2+ handling in human prostate cancer cells

The effects of triethyltin on Ca2+ mobilization in human PC3 prostate cancer cells have been explored. Triethyltin increased [Ca2+](i) at concentrations larger than 3 muM with an EC50 of 30 muM. Within 5 min, the [Ca2+](i) signal was composed of a gradual rise and a sustained phase. The [Ca2+](i) signal was reduced by half by removing extracellular Ca2+. The triethyltin-induced [Ca2+](i) increases were inhibited by 40% by 10 muM nifedipine, nimodipine and nicardipine, but were not affected by 10 muM of verapamil or diltiazem. In Ca2+-free medium, pretreatment with thapsigargin (1 muM), an endoplasmic reticulum Ca2+ pump inhibitor, reduced 200 muM triethyltin-induced Ca2+ increases by 50%. Pretreatment with U73122 (2 muM) to inhibit phospholipase C did not alter 200 muM triethyltin-induced [Ca2+](i) increases. Incubation with triethyltin at a concentration that did not increase [Ca2+](i) (1 muM) in Ca2+-containing medium for 3 min potentiated ATP (10 muM)- or bradykinin (1 muM)-induced [Ca2+](i) increases by 41 +/- 3% and 51 +/- 2%, respectively. Collectively, this study shows that the environmental toxicant triethyltin altered Ca2+ handling in PC3 prostate cancer cells in a concentration-dependent manner: at higher concentrations it increased basal [Ca2+](i); and at lower concentrations it potentiated agonists-induced [Ca2+](i) increases. (C) 2002 Elsevier Science Inc. All rights reserved.