Takahashi_2000_Prostate_44_328

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 therapy by controlling the malignancy of tumor cells through the induction of differentiation in vitro.
METHODS: We examined the ability of staurosporine to induce differentiation of human prostate cancer TSU-Pr1 cells into the cells with neuronal characteristics.
RESULTS: At low concentrations, staurosporine remarkably suppressed proliferation of human prostate cancer TSU-Pr1 cells without increasing dead cell number. TSU-Pr1 cells treated with 10(-8) M staurosporine began to extend neurites within 1 day, and approximately 80% of cells were changed to a neuronal morphology at 3 days. The expression of mRNA of tau, a microtubule-associated protein that is one of the essential components of neurite outgrowth, time-dependently increased in the cells treated with 10(-8) M staurosporine. Similarly, the amount of acetylcholinesterase increased. Colony-forming activity of TSU-Pr1 cells treated with 10(-8) M staurosporine for 7 days was 40% that of control cells. The invasive ability of TSU-Pr1 cells treated with staurosporine to penetrate through a reconstituted basement membrane of Matrigel was 20% that of untreated cells.
CONCLUSIONS: These results suggest that staurosporine might induce differentiation of human prostate cancer TSU-Pr1 cells to cells with neuronal characteristics.