Defining characteristics of Types I and II apoptotic cells in response to TRAIL

Neoplasia. Nov-Dec 2002;4(6):551-7. doi: 10.1038/sj.neo.7900270.

Abstract

Type I cells have been defined to be independent of mitochondria for the induction of Fas death receptor-mediated apoptosis, whereas Type II cells are mitochondria-dependent. Knock-out studies in mice show that thymocytes are Type I and liver cells are Type II. We have previously shown that primary human hepatocytes and HCT116 human colon carcinoma cells behave like Type II cells because TRAIL-induced apoptosis can be blocked by the caspase 9 inhibitor, Z-LEHD-FMK. On the other hand, caspase 9 inhibition does not allow survival of TRAIL-treated SW480 colon cancer cells, which is predicted for Type I cells. Investigating the differences in TRAIL-induced apoptotic pathways in HCT116 and SW480 cells revealed that although FADD, BID, and procaspase 3 protein levels are higher in SW480 cells, and although procaspase 8 and FLIP processing is more efficient at the TRAIL-DISC of SW480 cells, BID, procaspase 3, XIAP, and PARP cleavages occur more rapidly in HCT116, despite the higher levels of BCL-2 and HSP70. Cytochrome c release from the mitochondria to the cytoplasm is more efficient in HCT116 cells. These results suggest BID cleavage as a possible limiting factor in the involvement of mitochondria in TRAIL-induced cell death. Thus, regulation of BID cleavage may define if a cell is mitochondria-dependent or -independent in response to TRAIL death receptor-induced apoptosis.

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins
  • Arabidopsis Proteins*
  • BH3 Interacting Domain Death Agonist Protein
  • Blotting, Western
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carrier Proteins / metabolism*
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Child
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Cytochrome c Group / metabolism
  • Enzyme Precursors / metabolism
  • Fatty Acid Desaturases / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Hepatocytes / cytology
  • Hepatocytes / enzymology*
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Membrane Glycoproteins / pharmacology*
  • Mitochondria / physiology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Precipitin Tests
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Subcellular Fractions
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Apoptosis Regulatory Proteins
  • Arabidopsis 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
  • Enzyme Precursors
  • HSP70 Heat-Shock Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9
  • Caspases