期刊
NATURAL COMPOUNDS AND THEIR ROLE IN APOPTOTIC CELL SIGNALING PATHWAYS
卷 1171, 期 -, 页码 156-162出版社
WILEY-BLACKWELL
DOI: 10.1111/j.1749-6632.2009.04711.x
关键词
beta-carotene; ataxia-telangiectasia-mutated; apoptosis
资金
- Korea Science and Engineering Foundation [F01-2006-000-10063-0]
- Korea Government (Ministry of Science and Technology) [R11-2007-040-010020]
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 mu mol/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 antiapoptotic 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.
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