INDUCTION OF APOPTOSIS IN PROSTATIC TUMOR-CELL LINE DU145 BY STAUROSPORINE, A POTENT INHIBITOR OF PROTEIN-KINASES

We are interested in studying the possibility of modulating prostatic cell growth by manipulating apoptosis. Here we show that 1 mu M stauro sporine (STS) induces a human androgen-independent prostatic tumor cel l line, DU145, to undergo dramatic changes in morphology and results i n programmed cell death. Several genes involved in apoptosis were anal yzed for expression in STS-treated and untreated DU145 cells. It was o bserved that these genes were differentially regulated. The expression level of bcl-2 bcl-xL, Ich-1L remains unchanged in treated and untrea ted cells. On the other hand, DAD1 and interleukin-1 beta-converting e nzyme (ICE) were downregulated while bcl-xs and Ich-1s were upregulate d. By blocking bcl-2 gene expression using antisense oligonucleotides, it was determined that the anti-bcl-2 oligonucleotides have no effect on the proliferation of DU145 or STS-treated DU145 cells. These resul ts demonstrate that programmed cell death can be induced in an androge n-independent prostatic cancer cell line and BCL-2 was found not to pl ay an important role in preventing STS-induced apoptosis in the DU145 cell line. (C) 1996 Wiley-Liss, Inc.