Growth-inhibitory effects of serotonin uptake inhibitors on human prostate carcinoma cell lines

Growth stimulation of a variety of cell types by the neurotransmitter serotonin has been reported. We have examined the effects of three serotonin-uptake inhibitors, 6-nitroquipazine, zimelidine and fluoxetine (Prozac, Eli Lilly Co., Indianapolis, Indiana) on human prostate carcinoma cell lines. In vitro, all 3 of these compounds inhibited the proliferation of PC-3, DU-145 and LNCaP cells in a dose-dependent manner. Also, all 3 compounds blocked the uptake of a radiolabeled analog of serotonin by the prostate carcinoma cell lines. The order of potency for inhibition of growth as well as for serotonin uptake was fluoxetine > zimelidine > 6-nitroquipazine. The growth of subcutaneous, PC-3 xenografts in athymic nude mice was significantly inhibited by fluoxetine. These results implicate biogenic amines such as serotonin in the growth of prostate carcinoma cells and indicate the potential use of serotonin-uptake inhibitors for the treatment of prostate cancer.