Protective effect of L-carnosine against 12-O-tetradecanoylphorbol-13-acetate- or hydrogen peroxide-induced apoptosis on v-myc transformed rat liver epithelial cells

Cancer Lett. 2002 Apr 8;178(1):53-62. doi: 10.1016/s0304-3835(01)00821-7.

Abstract

Apoptotic processes have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease etc. beta-Alanyl-L-histidine (L-carnosine), occurring abundantly in skeletal muscles has been suggested to possess antioxidative activity. We investigated whether L-carnosine prevents 12-O-tetradecanoylphorbol-13-acetate (TPA)- or hydrogen peroxide (H2O2)-induced apoptosis involving mitochondria in the v-myc transformed rat liver epithelial cells (WB-myc cells). L-Carnosine prevented both TPA- and H2O2-induced DNA fragmentation, the loss of mitochondrial membrane potentials and blocked the release of cytochrome c into cytosol. Subsequently, the cleavages of poly (ADP-ribose) polymerase were significantly reduced in L-carnosine-treated cells. However, western blotting analysis revealed that p53 protein level did not change for 12h after TPA- and H2O2-treatment. Therefore, these results suggested that L-carnosine, an antioxidant, protected both H2O2- and TPA-induced apoptosis through mitochondrial pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Bisbenzimidazole
  • Blotting, Western
  • Carnosine / pharmacology*
  • Cell Line, Transformed / drug effects
  • Cells, Cultured
  • Cytochrome c Group / metabolism
  • Cytosol / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Genes, myc / physiology*
  • Hydrogen Peroxide / toxicity*
  • Liver / drug effects*
  • Liver / metabolism
  • Microscopy, Fluorescence
  • Poly(ADP-ribose) Polymerases / metabolism
  • Rats
  • Rhodamine 123
  • Tetradecanoylphorbol Acetate / toxicity*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cytochrome c Group
  • Tumor Suppressor Protein p53
  • Rhodamine 123
  • Carnosine
  • Hydrogen Peroxide
  • Poly(ADP-ribose) Polymerases
  • Bisbenzimidazole
  • Tetradecanoylphorbol Acetate