Desipramine-induced Ca2+ movement and cytotoxicity in PC3 human prostate cancer cells.
The effect of the antidepressant desipramine on intracellular Ca(2+) movement and viability in prostate cancer cells has not been explored previously. The present study examined whether desipramine could alter Ca(2+) handling and viability in human prostate PC3 cancer cells. Cytosolic free Ca(2+) levels ([Ca(2+)](i)) in populations of cells were measured using fura-2 as a probe. Desipramine at concentrations above 10 microM increased [Ca(2+)](i) in a concentration-dependent manner. The responses saturated at 300 microM desipramine. The Ca(2+) signal was reduced by half by removing extracellular Ca(2+), but was unaffected by nifedipine, nicardipine, nimodipine, diltiazem or verapamil. In Ca(2+)-free medium, after treatment with 300 microM desipramine, 1 microM thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) failed to release Ca(2+) from endoplasmic reticulum. Conversely, desipramine failed to release more Ca(2+) after thapsigargin treatment. Inhibition of phospholipase C with U73122 did not affect desipramine-induced Ca(2+) release. Overnight incubation with 10-800 microM desipramine decreased viability in a concentration-dependent manner. Chelation of cytosolic Ca(2+) with BAPTA did not reverse the decreased cell viability. Collectively, the data suggest that in PC3 cells, desipramine induced a [Ca(2+)](i) increase by causing Ca(2+) release from endoplasmic reticulum in a phospholipase C-independent fashion and by inducing Ca(2+) influx. Desipramine decreased cell viability in a concentration-dependent, Ca(2+)-independent manner.
Huang
Chun-Jen
CJ
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Cheng
He-Hsiung
HH
Chou
Chiang-Ting
CT
Kuo
Chun-Chi
CC
Lu
Yih-Chau
YC
Tseng
Li-Ling
LL
Chu
Sau-Tung
ST
Hsu
Shu-Shong
SS
Wang
Jue-Long
JL
Lin
Ko-Long
KL
Chen
I-Shu
IS
Liu
Shiuh-Inn
SI
Jan
Chung-Ren
CR
D000928:Antidepressive Agents / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D003891:Desipramine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016257:Fura-2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019284:Thapsigargin / Q000494:pharmacology
D000928:Antidepressive Agents; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D019284:Thapsigargin; D002118:Calcium; D003891:Desipramine; D016257:Fura-2