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 μM with an EC₅₀ of 30 μM. 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 μM nifedipine, nimodipine and nicardipine, but were not affected by 10 μM of verapamil or diltiazem. In Ca²⁺-free medium, pretreatment with thapsigargin (1 μM), an endoplasmic reticulum Ca²⁺ pump inhibitor, reduced 200 μM triethyltin-induced Ca²⁺ increases by 50%. Pretreatment with U73122 (2 μM) to inhibit phospholipase C did not alter 200 μM triethyltin-induced [Ca²⁺]_i increases. Incubation with triethyltin at a concentration that did not increase [Ca²⁺]_i (1 μM) in Ca²⁺-containing medium for 3 min potentiated ATP (10 μM)- or bradykinin (1 μM)-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.