Mechanism of β‐Carotene‐Induced Apoptosis of Gastric Cancer Cells: Involvement of Ataxia‐Telangiectasia‐Mutated

β‐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 β‐carotene induces apoptosis of gastric adenocarcinoma (AGS) cells and whether ATM is involved in β‐carotene‐induced apoptosis of AGS cells. We found that β‐carotene (100 μmol/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 β‐carotene in AGS cells. β‐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, β‐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 β‐carotene‐induced apoptosis of gastric cancer cells.