Induction of apoptosis in prostatic tumor cell line DU145 by staurosporine, a potent inhibitor of protein kinases

Prostate. 1996 Aug;29(2):69-76. doi: 10.1002/(SICI)1097-0045(199608)29:2<69::AID-PROS1>3.0.CO;2-C.

Abstract

We are interested in studying the possibility of modulating prostatic cell growth by manipulating apoptosis. Here we show that 1 microM staurosporine (STS) induces a human androgen-independent prostatic tumor cell line, DU145, to undergo dramatic changes in morphology and results in programmed cell death. Several genes involved in apoptosis were analyzed for expression in STS-treated and untreated DU145 cells. It was observed that these genes were differentially regulated. The expression level of bcl-2, bcl-xL, Ich-1L remains unchanged in treated and untreated cells. On the other hand, DAD1 and interleukin-1 beta-converting enzyme (ICE) were downregulated while bcl-xs and Ich-1s were upregulated. 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 results demonstrate that programmed cell death can be induced in an androgen-independent prostatic cancer cell line and BCL-2 was found not to play an important role in preventing STS-induced apoptosis in the DU145 cell line.

MeSH terms

  • Alkaloids / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins
  • Base Sequence
  • Caenorhabditis elegans Proteins*
  • Carcinoma / chemistry
  • Carcinoma / pathology*
  • Carcinoma / physiopathology
  • Caspase 2
  • Caspases*
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / genetics
  • Down-Regulation
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Molecular Sequence Data
  • Oligonucleotides / analysis
  • Oligonucleotides / chemistry
  • Oligonucleotides / genetics
  • Polymerase Chain Reaction
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / physiopathology
  • Protein Kinase Inhibitors*
  • Proteins / analysis
  • Proteins / genetics
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics
  • Staurosporine
  • Time Factors
  • Tumor Cells, Cultured
  • Up-Regulation
  • bcl-2-Associated X Protein
  • bcl-X Protein

Substances

  • Alkaloids
  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • Caenorhabditis elegans Proteins
  • DNA, Neoplasm
  • Dad-1 protein, C elegans
  • Enzyme Inhibitors
  • Oligonucleotides
  • Protein Kinase Inhibitors
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Repressor Proteins
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • Caspase 2
  • Caspases
  • Staurosporine