Low-dose staurosporine suppresses proliferation and induces neurites in human prostatic cancer TSU-Pr1 cells

BACKGROUND. Despite the beneficial effects of androgen ablation therapy in patients with prostate carcinoma, advancing prostate cancer usually becomes hormone-refractory. We attempted to establish a new prostate cancer therap y by controlling the malignancy of tumor cells through the induction of dif ferentiation in vitro. METHODS. We examined the ability of staurosporine to induce differentiation of human prostate cancer TSU-Prl cells into the cells with neuronal charac teristics. RESULTS. At low concentrations, staurosporine remarkably suppressed prolife ration of human prostate cancer TSU-Prl cells without increasing dead cell number. TSU-Prl cells treated with 10(-8) M staurosporine began to extend n eurites within 1 day, and approximately 80% of cells were changed to a neur onal morphology at 3 days. The expression of mRNA of tau, a microtubule-ass ociated protein that is one of the essential components of neurite outgrowt h, time-dependently increased in the cells treated with 10-8 M staurosporin e. Similarly, the amount of acetylcholinesterase increased. Colony-forming activity of TSU-rrl cells treated with 10-8 M staurosporine for 7 days was 40% that of control cells. The invasive ability of TSU-Prl cells treated wi th staurosporine to penetrate through a reconstituted basement membrane of Matrigel was 20% that of untreated cells. CONCLUSIONS. These results suggest that staurosporine might induce differen tiation of human prostate cancer TSU-Prl cells to cells with neuronal chara cteristics. (C) 2000 Wiley-Liss, Inc.