TRAIL (APO-2L) induces apoptosis in human prostate cancer cells that is inhibitable by Bcl-2

Oncogene. 2001 Jun 28;20(29):3757-65. doi: 10.1038/sj.onc.1204504.


To determine if TRAIL-induced apoptosis in human prostate tumor cells was suppressed by bcl-2, we compared the levels of apoptosis induced by recombinant human TRAIL in pairs of isogenic cell lines that do or do not express bcl-2. Three human prostate tumor cell lines (PC3, DU145 and LNCaP) and their bcl-2-expressing counterparts were tested for their susceptibility to TRAIL. Cells were exposed to TRAIL in the presence of cycloheximide which acted as a sensitizer. Apoptosis was induced rapidly in PC3 and DU145 neo-control transfected cells, whereas induction in LNCaP required 24 h. All three cell line variants expressing bcl-2 were resistant to the apoptotic effects of TRAIL. Caspase 3 and 8 activation was also detected in the neo control cells after treatment with TRAIL, demonstrating the rapid activation of the caspase cascade similar to that seen with other death receptors. Bcl-2 overexpression in these cells blocked activation of these caspases, suggesting that bcl-2 expression of human cancer cells may be a critical factor in the therapeutic efficacy of TRAIL.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism
  • Caspases / metabolism
  • Cycloheximide / pharmacology
  • Cytochrome c Group / metabolism
  • Enzyme Activation
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Ligands
  • Male
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / metabolism
  • Membrane Glycoproteins / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Protein Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*


  • Antineoplastic Agents
  • Apoptosis Regulatory Proteins
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Carrier Proteins
  • Cytochrome c Group
  • Intracellular Signaling Peptides and Proteins
  • Ligands
  • Membrane Glycoproteins
  • Protein Synthesis Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Cycloheximide
  • Caspases