Effect of the antidepressant maprotiline on Ca2+ movement and proliferation in human prostate cancer cells |
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Authors: | Hsu Shu-Shong Chen Wei-Chuan Lo Yuk-Keung Cheng Jin-Shiung Yeh Jeng-Hsien Cheng He-Hsing Chen Jin-Shyr Chang Hong-Tai Jiann Bang-Ping Huang Jong-Khing Jan Chung-Ren |
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Institution: | Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan. |
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Abstract: | 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. |
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Keywords: | Ca2+ stores fura-2 maprotiline PC3 prostate tetrazolium |
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