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.