Mechanism of beta-carotene-induced apoptosis of gastric cancer cells: involvement of ataxia-telangiectasia-mutated

Ann N Y Acad Sci. 2009 Aug:1171:156-62. doi: 10.1111/j.1749-6632.2009.04711.x.


Beta-carotene acts as an antioxidant or a pro-oxidant depending on the concentrations that cells are treated with. Oxidative DNA damage is related to apoptosis of various cells. Ataxia-telangiectasia-mutated (ATM), a sensor for DNA-damaging agents, activates a variety of effectors in multiple signaling pathways, such as DNA repair and apoptosis. In the present study, we investigated whether a high concentration of beta-carotene induces apoptosis of gastric adenocarcinoma (AGS) cells and whether ATM is involved in beta-carotene-induced apoptosis of AGS cells. We found that beta-carotene (100 micromol/L) induced apoptosis (determined by cell viability), DNA fragmentation, and the protein levels of p53 and Bcl-2 in AGS cells. ATM levels in the nucleus decreased from beta-carotene in AGS cells. beta-Carotene-induced alterations, including an increase in DNA fragmentation and p53 levels and a decrease in nuclear ATM and cellular Bcl-2 levels, were inhibited in the cells transfected with full-length ATM cDNA compared to wild-type cells or the cells transfected with control vector plasmid control DNA vector (pcDNA). In conclusion, beta-carotene induces apoptosis by increasing apoptotic protein p53 and decreasing anti-apoptotic Bcl-2 as well as nuclear ATM in AGS cells. Nuclear loss of ATM may be the underlying mechanism of beta-carotene-induced apoptosis of gastric cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Ataxia Telangiectasia Mutated Proteins
  • Blotting, Western
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • DNA Fragmentation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Vitamins / pharmacology
  • beta Carotene / pharmacology*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Vitamins
  • beta Carotene
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases