Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis
In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(<i>R</i>)-AD-1, 20(<i>R</i>)-AD-2, 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2) were investigated. The results indicated that all of the four compounds obv...
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MDPI AG
2023-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/18/6698 |
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| author | Xude Wang Meng Ding Hong Zhao Mengru Zhou Xuan Lu Yuanyuan Sun Qinggao Zhang Yuqing Zhao Ruoyu Wang |
| author_facet | Xude Wang Meng Ding Hong Zhao Mengru Zhou Xuan Lu Yuanyuan Sun Qinggao Zhang Yuqing Zhao Ruoyu Wang |
| author_sort | Xude Wang |
| collection | DOAJ |
| description | In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(<i>R</i>)-AD-1, 20(<i>R</i>)-AD-2, 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 was significantly better than 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2 barely exhibited the same results. The results indicated that 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 as potential agents for human gastric carcinoma therapy. |
| first_indexed | 2024-03-10T22:23:52Z |
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| language | English |
| last_indexed | 2024-03-10T22:23:52Z |
| publishDate | 2023-09-01 |
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| series | Molecules |
| spelling | doaj.art-1d569b40b7cb4b12badf9e5726db94622023-11-19T12:11:11ZengMDPI AGMolecules1420-30492023-09-012818669810.3390/molecules28186698Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell ApoptosisXude Wang0Meng Ding1Hong Zhao2Mengru Zhou3Xuan Lu4Yuanyuan Sun5Qinggao Zhang6Yuqing Zhao7Ruoyu Wang8Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, ChinaCollege of Chemistry and Chemical Engineering, Cangzhou Normal University, Cangzhou 061000, ChinaChina College of Life and Health, Dalian University, Dalian 116622, ChinaChronic Disease Research Center, Medical College, Dalian University, Dalian 116622, ChinaChina College of Life and Health, Dalian University, Dalian 116622, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji 133002, ChinaSchool of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, ChinaIn this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(<i>R</i>)-AD-1, 20(<i>R</i>)-AD-2, 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 was significantly better than 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(<i>S</i>)-AD-1 and 20(<i>S</i>)-AD-2 barely exhibited the same results. The results indicated that 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(<i>R</i>)-AD-1 and 20(<i>R</i>)-AD-2 as potential agents for human gastric carcinoma therapy.https://www.mdpi.com/1420-3049/28/18/6698AD-1 and AD-2isomersanti-cancerapoptosisROS |
| spellingShingle | Xude Wang Meng Ding Hong Zhao Mengru Zhou Xuan Lu Yuanyuan Sun Qinggao Zhang Yuqing Zhao Ruoyu Wang Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis Molecules AD-1 and AD-2 isomers anti-cancer apoptosis ROS |
| title | Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis |
| title_full | Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis |
| title_fullStr | Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis |
| title_full_unstemmed | Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis |
| title_short | Stereospecificity of Ginsenoside AD-1 and AD-2 Showed Anticancer Activity via Inducing Mitochondrial Dysfunction and Reactive Oxygen Species Mediate Cell Apoptosis |
| title_sort | stereospecificity of ginsenoside ad 1 and ad 2 showed anticancer activity via inducing mitochondrial dysfunction and reactive oxygen species mediate cell apoptosis |
| topic | AD-1 and AD-2 isomers anti-cancer apoptosis ROS |
| url | https://www.mdpi.com/1420-3049/28/18/6698 |
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