Protein kinase C delta is not activated by caspase-3 and its inhibition is sufficient to induce apoptosis in the colon cancer line, COLO 205

Cell Signal. 2005 Feb;17(2):253-62. doi: 10.1016/j.cellsig.2004.07.005.

Abstract

Activation of protein kinase C delta (PKCdelta) is believed to be pro-apoptotic. PKCdelta is reported to be reduced in colon cancers. Using a colon cancer cell line, COLO 205, we have examined the roles of PKCdelta in apoptosis and of caspase-3 in the activation and inhibition of PKCdelta. PKCdelta activation with bistratene A and its inhibition with rottlerin induced apoptosis. Effects of PKC activators and inhibitors were additive, suggesting that PKCdelta down-regulation was responsible for the effects on apoptosis. Different apoptotic pathways induced PKCdelta cleavage, but the fragment produced was inactive in kinase assays. Caspase-3 inhibition did not block DNA fragmentation or PKCdelta proteolysis despite blocking intracellular caspase-3 activity. Calpain inhibition with calpeptin did not prevent TPA-induced PKCdelta cleavage. We conclude that in colonocytes, inhibition of PKCdelta is sufficient to lead to caspase-3-independent apoptosis. Caspase-3 does not cleave PKCdelta to an active form, nor does caspase-3 inhibition block apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / pharmacology
  • Acetophenones / pharmacology
  • Alkaloids
  • Amino Acid Chloromethyl Ketones / pharmacology
  • Antineoplastic Agents / pharmacology
  • Apoptosis*
  • Benzophenanthridines
  • Benzopyrans / pharmacology
  • Calpain / antagonists & inhibitors
  • Caspase 3
  • Caspase Inhibitors
  • Caspases / metabolism
  • Caspases / physiology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / chemistry
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA Fragmentation / drug effects
  • Dipeptides / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Flow Cytometry
  • Histones / metabolism
  • Humans
  • Indomethacin / pharmacology
  • Kinetics
  • Phenanthridines / pharmacology
  • Phosphorylation / drug effects
  • Protein Kinase C / metabolism
  • Protein Kinase C / physiology*
  • Protein Kinase C-delta
  • Pyrans / pharmacology
  • Spiro Compounds / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Acetamides
  • Acetophenones
  • Alkaloids
  • Amino Acid Chloromethyl Ketones
  • Antineoplastic Agents
  • Benzophenanthridines
  • Benzopyrans
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Dipeptides
  • Enzyme Inhibitors
  • Histones
  • Phenanthridines
  • Pyrans
  • Spiro Compounds
  • Tumor Necrosis Factor-alpha
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • bistratene A
  • calpeptin
  • rottlerin
  • chelerythrine
  • PRKCD protein, human
  • Protein Kinase C
  • Protein Kinase C-delta
  • CASP3 protein, human
  • Calpain
  • Caspase 3
  • Caspases
  • Tetradecanoylphorbol Acetate
  • Indomethacin