Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer
Name
ECAM.2014.436863.pdf
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7.35 MB
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Adobe PDF
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1648a46c41efa88a3e6b00c4d350ebfb
Author(s)
Chen, Kuan-Chung
Chen, Hsin-Yi
Chen, Calvin Yu-Chian
Date Issued
April 2014
Journal
Evidence-Based Complementary and Alternative Medicine
Publisher
Hindawi Publishing Corporation
Citation
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.
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
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Creative Commons Attribution
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DOI of Published Version
https://doi.org/10.1155/2014/436863
