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 µmol/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 Ca2+-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2+-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 µmol/L maprotiline did not alter cell proliferation, although incubation with 30–50 µmol/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.
Document Type: Research Article
Affiliations: 1: Department of Surgery, Ping Tung Christian Hospital, Ping Tung, Taiwan 2: Medicine and 3: Surgery, 4: Medical Education and Research, Kaohsiung Veterans General Hospital,
Publication date: July 1, 2004