tosylphenylalanyl-chloromethyl-ketone and Prostatic-Neoplasms

tosylphenylalanyl-chloromethyl-ketone has been researched along with Prostatic-Neoplasms* in 2 studies

Other Studies

2 other study(ies) available for tosylphenylalanyl-chloromethyl-ketone and Prostatic-Neoplasms

ArticleYear
Multiple effects of N-alpha-tosyl-L-phenylalanyl chloromethyl ketone (TPCK) on apoptotic pathways in human prostatic carcinoma cell lines.
    Cancer biology & therapy, 2004, Volume: 3, Issue:8

    TPCK is widely used as an inhibitor of chymotrypsin-like proteases but has recently been identified as an inhibitor of the PDK1/Akt pathway. In this study, we show that TPCK inhibits TRAIL-induced caspase activity but potentiates wortmannin-dependent caspase activity in prostatic carcinoma cell lines. The inhibitory activity of TPCK was found to be death ligand-specific since TPCK inhibits TRAIL-mediated caspase activity but does not affect Fas-induced caspase activity. Our data also show that impaired TRAIL-DISC formation in the presence of TPCK is responsible for caspase inhibition. Further, TPCK induces p53 expression and inhibits the PDK1/Akt pathway resulting in BAD dephosphorylation, and the release of cytochrome c and Smac/DIABLO from mitochondria. TPCK also selectively decreases the levels of androgen receptor and caspase-2 whereas it does not change the levels of other proteins (caspases-3, -7, -8, -9; heat shock proteins 27, 70, 90). Finally, TPCK-induced degradation of caspase-2 is protected by Bcl-2 overexpression, apparently by an adapter protein since direct interaction between caspase-2 and Bcl-2 was not detected. Together, these features suggest that TPCK could be used as a therapeutic agent for treatment of those tumor cells that are resistant to ligand-induced treatment because of aberrant signaling pathways downstream of the DISC.

    Topics: Alkylating Agents; Androstadienes; Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Caspases; Death Domain Receptor Signaling Adaptor Proteins; Humans; Male; Membrane Glycoproteins; Phosphoinositide-3 Kinase Inhibitors; Prostatic Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-bcl-2; Receptors, Tumor Necrosis Factor; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Tosylphenylalanyl Chloromethyl Ketone; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Wortmannin

2004
On the trail of cell death pathways in prostate cancer.
    Cancer biology & therapy, 2004, Volume: 3, Issue:8

    Topics: Alkylating Agents; Antineoplastic Agents; Apoptosis; Apoptosis Regulatory Proteins; Caspases; Humans; Male; Membrane Glycoproteins; Prostatic Neoplasms; Signal Transduction; TNF-Related Apoptosis-Inducing Ligand; Tosylphenylalanyl Chloromethyl Ketone; Tumor Necrosis Factor-alpha

2004