We reported previously that human prostate cancer cell line TSU-Pr1 can differentiate into neuronal cells by staurosporine treatment. In this process, reduction of invasive abilities was observed in staurosporine treated TSU-Pr1 cells. In the present study, we investigated the effect of staurosporine on tissue inhibitor of metalloproteinases (TIMPs) in prostate cancer cells. We show that treatment of TSU-Pr1 cells with staurosporine results in induction of TIMP-I mRNA and protein secretion. The induction of TIMP-I mRNA expression by staurosporine is likely to be caused by increased transcriptional activity and this mechanism is indirect. Furthermore, recombinant human TIMP-I reduces the invasive activity of TSU-Pr1 cells. We are the first to report that mRNA expression and protein secretion of TIMP-1 are enhanced by staurosporine treatment in prostate cancer cells. These findings suggest that enhancement of TIMP-1 is associated with suppression of invasive activity caused by staurosporine treatment. (C) 2002 Elsevier Science (USA). All rights reserved.