Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231

BioMed Research International

2014

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.

Section: Resultsmentioning

confidence: 99%

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

BioMed Research International

2014

“…The second ranked herb, Mucuna pruriens , can reduce oxidation and prevent Parkinson's disease [ 61 , 62 ]. The third ranked compound, abrine from the herb Abrus precatorius , has an immune-toxin [ 63 ] and can induce apoptosis [ 64 , 65 ]. As reported in the literature, most of these compounds can have an effect on immunity.…”

Section: Resultsmentioning

confidence: 99%

Lead Screening for HIV of C‐C Chemokine Receptor Type 5 Receptor Inhibited by Traditional Chinese Medicine

Hung

Evidence-Based Complementary and Alternative Medicine

Huang

et al. 2014

The acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), has become a serious world-wide problem because of this disease's rapid propagation and incurability. Recent research has pointed out that the C-C chemokine receptor type 5 (CCR5) is an important target for HIV infection. The traditional Chinese medicine (TCM) database (http://tcm.cmu.edu.tw/) has been screened for molecular compounds that, by simulating molecular docking and molecular dynamics, may protect CCR5 against HIV. Saussureamine C, 5-hydroxy-L-tryptophan, and abrine are selected based on the docking score being higher than Maraviroc and other TCM compounds. The molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond variations, this research surmises TRP86, TYR108, GLN194, TYR251, and GLU283 are the main regions of important amino acids in CCR5. In addition to the detection of TCM compound efficacy, we suggest saussureamine C is better than the others for maintaining protein composition during protein-ligand interaction, based on the structural variation.

“…The second ranked compounds with the herb do not have reference about immunity. The third ranked herb Abrus precatorius had been defined the relation about Antiprotozoal [ 52 , 53 ], antimicrobial [ 54 – 56 ], anti-inflammatory [ 57 ], apoptosis [ 58 , 59 ], and immunotoxin [ 60 ]. Most of the reported literatures indicate that these compounds can have an effect on immunity; therefore we suggest that the selected compounds can have an influence on MX2.…”

Section: Resultsmentioning

confidence: 99%

Insight into HIV of IFN-Induced Myxovirus Resistance 2 (MX2) Expressed by Traditional Chinese Medicine

Hung

BioMed Research International

Chan

et al. 2014

Recently, an important topic of the acquired immunodeficiency syndrome (AIDS) had been published in 2013. In this report, the expression of the IFN-induced myxovirus resistance 2 (MX2) had been defined the function to kill the human immunodeficiency virus (HIV). The screening from the Traditional Chinese Medicine (TCM) database by simulating molecular docking and molecular dynamics could select candidate compounds, which may express MX2 against HIV. Saussureamine C, Crotalaburnine, and Precatorine are selected based on the highest docking score and other TCM compounds. The data from molecular dynamics are helpful in the analysis and detection of protein-ligand interactions. According to the docking poses, hydrophobic interactions, and hydrogen bond with structure variations, this research could assess the interaction between protein and ligand interaction. In addition to the detection of TCM compound efficacy, we suggest that Saussureamine C is better than the others in protein-ligand interaction and the structural variation to express MX2.