Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in human prostate cancer cells.
1. The effect of maprotiline, an antidepressant, on human prostate cells is unclear. In the present study, the effect of maprotiline on [Ca2+]i and growth in PC3 human prostate cancer cells was measured using the fluorescent dyes fura-2 and tetrazolium, respectively. 2. Maprotiline caused a rapid, concentration-dependent increase in [Ca2+]i (EC50 = 200 micromol/L). The maprotiline-induced [Ca2+]i increase was reduced by removal of extracellular Ca2+ or pretreatment with nicardipine. 3. The maprotiline-induced Mn2+ influx-associated fura-2 fluorescence quench directly suggests that maprotiline caused Ca2+ influx. 4. In Ca(2+)-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+)-ATPase, caused a monophasic [Ca2+]i increase, after which the effects of maprotiline of increasing [Ca2+]i were abolished. In addition, pretreatment with maprotiline reduced a major portion of the thapsigargin-induced increase in [Ca2+]i. 5. U73122, an inhibitor of phospholipase C, abolished the ATP (but not maprotiline)-induced increase in [Ca2+]i. 6. Overnight incubation with 1-10 micromol/L maprotiline did not alter cell proliferation, although incubation with 30-50 micromol/L maprotiline decreased cell proliferation. 7, These findings suggest that maprotiline rapidly increases [Ca2+]i in human prostate cancer cells by stimulating both extracellular Ca2+ influx and intracellular Ca2+ release and that it may modulate cell proliferation in a concentration-dependent manner.
Hsu
Shu-Shong
SS
Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Chen
Wei-Chuan
WC
Lo
Yuk-Keung
YK
Cheng
Jin-Shiung
JS
Yeh
Jeng-Hsien
JH
Cheng
He-Hsing
HH
Chen
Jin-Shyr
JS
Chang
Hong-Tai
HT
Jiann
Bang-Ping
BP
Huang
Jong-Khing
JK
Jan
Chung-Ren
CR
D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005456:Fluorescent Dyes; D016257:Fura-2; D006801:Humans; D008297:Male; D008376:Maprotiline / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010738:Type C Phospholipases / Q000378:metabolism
D018687:Antidepressive Agents, Second-Generation; D005456:Fluorescent Dyes; D008376:Maprotiline; D010738:Type C Phospholipases; D002118:Calcium; D016257:Fura-2