Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer
Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B s...
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| Format: | Article |
| Language: | English |
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Hindawi Publishing Corporation
2015
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| Online Access: | http://hdl.handle.net/1721.1/96094 |
| _version_ | 1811077031760232448 |
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| author | Chen, Kuan-Chung Chen, Hsin-Yi Chen, Calvin Yu-Chian |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Chen, Kuan-Chung Chen, Hsin-Yi Chen, Calvin Yu-Chian |
| author_sort | Chen, Kuan-Chung |
| collection | MIT |
| description | Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A-α protein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A-α protein. |
| first_indexed | 2024-09-23T10:36:36Z |
| format | Article |
| id | mit-1721.1/96094 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:36:36Z |
| publishDate | 2015 |
| publisher | Hindawi Publishing Corporation |
| record_format | dspace |
| spelling | mit-1721.1/960942022-09-27T10:02:21Z Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer Chen, Kuan-Chung Chen, Hsin-Yi Chen, Calvin Yu-Chian Massachusetts Institute of Technology. Computational and Systems Biology Program Chen, Calvin Yu-Chian Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A-α protein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A-α protein. National Science Council of Taiwan (NSC102-2325-B039-001) National Science Council of Taiwan (NSC102-2221-E-468-027-) Asia University (Taiwan) (Asia101-CMU- 2, 102-Asia-07) China Medical University (Hospital, DMR-103-058) China Medical University (Hospital, DMR-103-001) China Medical University (Hospital, DMR-103-096) Taiwan Department of Health. Clinical Trial and Research Center of Excellence Taiwan Department of Health. Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004) Taiwan Department of Health. Clinical Trial and Research Center of Excellence (MOHW103-TD-B-111-03) 2015-03-19T20:22:00Z 2015-03-19T20:22:00Z 2014-04 2014-01 2015-03-19T11:33:30Z Article http://purl.org/eprint/type/JournalArticle 1741-427X 1741-4288 Article ID 436863 http://hdl.handle.net/1721.1/96094 Chen, Kuan-Chung, Hsin-Yi Chen, and Calvin Yu-Chian Chen. "Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer." Evidence-Based Complementary and Alternative Medicine Volume 2014 (2014), Article ID 436863, 10 p. en http://dx.doi.org/10.1155/2014/436863 Evidence-Based Complementary and Alternative Medicine Creative Commons Attribution http://creativecommons.org/licenses/by/2.0 Copyright © 2014 Kuan-Chung Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. application/pdf Hindawi Publishing Corporation Hindawi Publishing Corporation |
| spellingShingle | Chen, Kuan-Chung Chen, Hsin-Yi Chen, Calvin Yu-Chian Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title | Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title_full | Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title_fullStr | Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title_full_unstemmed | Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title_short | Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer |
| title_sort | potential protein phosphatase 2a agents from traditional chinese medicine against cancer |
| url | http://hdl.handle.net/1721.1/96094 |
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