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 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.
Zhang
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Department 4MG, Aging and Degenerative Diseases Research, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Hoang
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Saeed
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Ng
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D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D029742:Caenorhabditis elegans Proteins; D002277:Carcinoma / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D053143:Caspase 2; D020169:Caspases; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004273:DNA, Neoplasm / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D016133:Polymerase Chain Reaction; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000503:physiopathology; D047428:Protein Kinase Inhibitors; D011506:Proteins / Q000032:analysis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins / Q000032:analysis / Q000235:genetics; D019311:Staurosporine; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D000470:Alkaloids; D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; D029742:Caenorhabditis elegans Proteins; D004273:DNA, Neoplasm; C096021:Dad-1 protein, C elegans; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D047428:Protein Kinase Inhibitors; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012097:Repressor Proteins; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D053143:Caspase 2; D020169:Caspases; D019311:Staurosporine