Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells
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 <i>Gynura procumbens</i>. In this study, the mechanism of cancer cell death induc...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/8894 |
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| author | Hun Hwan Kim Se Hyo Jeong Sang Eun Ha Min Yeong Park Pritam Bhagwan Bhosale Abuyaseer Abusaliya Chung Kil Won Jeong Doo Heo Hyun Wook Kim Gon Sup Kim |
| author_facet | Hun Hwan Kim Se Hyo Jeong Sang Eun Ha Min Yeong Park Pritam Bhagwan Bhosale Abuyaseer Abusaliya Chung Kil Won Jeong Doo Heo Hyun Wook Kim Gon Sup Kim |
| author_sort | Hun Hwan Kim |
| collection | DOAJ |
| description | 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 <i>Gynura procumbens</i>. 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. |
| first_indexed | 2024-03-09T04:20:41Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:20:41Z |
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| spelling | doaj.art-2b338ad3bed4404ba662ca7d5a04a6f52023-12-03T13:46:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316889410.3390/ijms23168894Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS CellsHun Hwan Kim0Se Hyo Jeong1Sang Eun Ha2Min Yeong Park3Pritam Bhagwan Bhosale4Abuyaseer Abusaliya5Chung Kil Won6Jeong Doo Heo7Hyun Wook Kim8Gon Sup Kim9Research Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaBiological Resources Research Group, Gyeongnam Department of Environment Toxicology and Chemistry, Korea Institute of Toxicology, 17 Jegok-gil, Jinju 52834, KoreaDivision of Animal Bioscience & Integrated Biotechnology, Jinju 52725, KoreaResearch Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, KoreaKynurenic 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 <i>Gynura procumbens</i>. 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.https://www.mdpi.com/1422-0067/23/16/8894kynurenic acidapoptosisgastric cancerphenolic compoundtreatment |
| spellingShingle | Hun Hwan Kim Se Hyo Jeong Sang Eun Ha Min Yeong Park Pritam Bhagwan Bhosale Abuyaseer Abusaliya Chung Kil Won Jeong Doo Heo Hyun Wook Kim Gon Sup Kim Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells International Journal of Molecular Sciences kynurenic acid apoptosis gastric cancer phenolic compound treatment |
| title | Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells |
| title_full | Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells |
| title_fullStr | Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells |
| title_full_unstemmed | Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells |
| title_short | Cellular Regulation of Kynurenic Acid-Induced Cell Apoptosis Pathways in AGS Cells |
| title_sort | cellular regulation of kynurenic acid induced cell apoptosis pathways in ags cells |
| topic | kynurenic acid apoptosis gastric cancer phenolic compound treatment |
| url | https://www.mdpi.com/1422-0067/23/16/8894 |
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