title: Mechanism of beta-carotene-induced apoptosis of gastric cancer cells: involvement of ataxia-telangiectasia-mutated.
abstract: 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.
authors.affiliation: Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Jang
authors.forename: Joo Weon
authors.initials: JW
authors.lastname: Lim
authors.forename: Hyeyoung
authors.initials: H
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D064007:Ataxia Telangiectasia Mutated Proteins; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D014815:Vitamins / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D014815:Vitamins; D019207:beta Carotene; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases