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 microM with an EC50 of 30 microM. 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 microM nifedipine, nimodipine and nicardipine, but were not affected by 10 microM of verapamil or diltiazem. In Ca2+-free medium, pretreatment with thapsigargin (1 microM), an endoplasmic reticulum Ca+ pump inhibitor, reduced 200 microM triethyltin-induced Ca+ increases by 50%. Pretreatment with U73122 (2 microM) to inhibit phospholipase C did not alter 200 microM triethyltin-induced [Ca2+]i increases. Incubation with triethyltin at a concentration that did not increase [Ca2+]i (1 microM) in Ca2+-containing medium for 3 min potentiated ATP (10 microM)- or bradykinin (1 microLM)-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.
Jan
Chung-Ren
CR
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Jiann
Bang-Ping
BP
Lu
Yih-Chau
YC
Chang
Hong-Tai
HT
Su
Warren
W
Chen
Wei-Chung
WC
Yu
Chia-Cheng
CC
Huang
Jong-Khing
JK
D002118:Calcium / Q000172:deficiency / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D016257:Fura-2 / Q000378:metabolism; D006801:Humans; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014267:Triethyltin Compounds / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D014267:Triethyltin Compounds; D009553:Nimodipine; C031575:triethyltin; D019284:Thapsigargin; D009529:Nicardipine; D000252:Calcium-Transporting ATPases; D009543:Nifedipine; D002118:Calcium; D016257:Fura-2