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BioMed Research International
Volume 2014, Article ID 364625, 10 pages
http://dx.doi.org/10.1155/2014/364625
Research Article

Potential Mitochondrial Isocitrate Dehydrogenase R140Q Mutant Inhibitor from Traditional Chinese Medicine against Cancers

1Department of Biomedical Informatics, Asia University, Taichung 41354, Taiwan
2School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan
3Department of Neurosurgery, China Medical University Hospital, Taichung 40447, Taiwan
4School of Pharmacy, China Medical University, Taichung 40402, Taiwan
5Research Center for Chinese Medicine & Acupuncture, China Medical University, Taichung 40402, Taiwan

Received 16 February 2014; Revised 4 March 2014; Accepted 4 March 2014; Published 5 June 2014

Academic Editor: Chung Y. Hsu

Copyright © 2014 Wen-Yuan Lee 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.

Abstract

A recent research of cancer has indicated that the mutant of isocitrate dehydrogenase 1 and 2 (IDH1 and 2) genes will induce various cancers, including chondrosarcoma, cholangiocarcinomas, and acute myelogenous leukemia due to the effect of point mutations in the active-site arginine residues of isocitrate dehydrogenase (IDH), such as IDH1/R132, IDH2/R140, and IDH2/R172. As the inhibition for those tumor-associated mutant IDH proteins may induce differentiation of those cancer cells, these tumor-associated mutant IDH proteins can be treated as a drug target proteins for a differentiation therapy against cancers. In this study, we aim to identify the potent TCM compounds from the TCM Database@Taiwan as lead compounds of IDH2 R140Q mutant inhibitor. Comparing to the IDH2 R140Q mutant protein inhibitor, AGI-6780, the top two TCM compounds, precatorine and abrine, have higher binding affinities with target protein in docking simulation. After MD simulation, the top two TCM compounds remain as the same docking poses under dynamic conditions. In addition, precatorine is extracted from Abrus precatorius L., which represents the cytotoxic and proapoptotic effects for breast cancer and several tumor lines. Hence, we propose the TCM compounds, precatorine and abrine, as potential candidates as lead compounds for further study in drug development process with the IDH2 R140Q mutant protein against cancer.