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 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.
Takahashi
N
N
Department of Hygiene-Chemistry, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
Shimizu
T
T
Takeda
K
K
D000110:Acetylcholinesterase / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D019311:Staurosporine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D016875:tau Proteins / Q000096:biosynthesis
D004791:Enzyme Inhibitors; D006131:Growth Inhibitors; D016875:tau Proteins; D000110:Acetylcholinesterase; D019311:Staurosporine