| Autor: |
Kim HH; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Jeong SH; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Ha SE; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.; Biological Resources Research Group, Gyeongnam Department of Environment Toxicology and Chemistry, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, Korea., Park MY; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Bhosale PB; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Abusaliya A; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Won CK; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea., Heo JD; Biological Resources Research Group, Gyeongnam Department of Environment Toxicology and Chemistry, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, Korea., Kim HW; Division of Animal Bioscience & Integrated Biotechnology, Jinju 52725, Korea., Kim GS; Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea. |
| Abstrakt: |
Kynurenic acid was included in the three compounds (caffeic acid, chlorogenic acid, and kynurenic acid) that showed high antioxidant and anti-inflammatory potential among the phenolic compounds contained in Gynura procumbens . In this study, the mechanism of cancer cell death induced by kynurenic acid (KYNA), which has the highest molecular binding affinity, in the gastric cancer cell line AGS was confirmed in molecular docking analysis. KYNA showed the most cancer cell death effect on AGS cells among several gastric cancer cell lines (MKN, AGS, and SNU). AGS cells were used for later experiments, and KYNA concentrations of 0, 150, 200, and 250 µM were used. KYNA inhibited cell migration and proliferation in AGS cells in a concentration-dependent manner. G2/M phase cell cycle arrest and reduction of related proteins (Cdc25C, CDK1 and CyclinB1) were confirmed in KYNA-treated AGS cells. Apoptosis of KYNA-treated AGS cells was confirmed by Annexin V/propidium iodide (PI) staining flow cytometry analysis. As a result of morphological chromatin condensation through DAPI (4',6-diamidino-2-phenylindole), intense blue fluorescence was confirmed. The mechanism of apoptosis induction of KYNA-treated AGS cells was confirmed by western blotting. In the extrinsic pathway, apoptosis induction markers FasL, Fas, and Caspase-3 and -8 were increased in a concentration-dependent manner upon KYNA treatment. In the intrinsic pathway, the expression of anti-apoptotic factors PI3K, AKT, and Bcl-xL was down-regulated, and the expression of apoptosis-inducing factors BAD, Bak, Bax, Cytochrom C, and Caspase-9 was up-regulated. Therefore, in the present study, we strongly imply that KYNA induces apoptosis in AGS gastric cancer cells. This suggests that KYNA, a natural compound, could be the basis for drug for the treatment of gastric cancer. |
