Prediction of anti-tumor chemical probes of a traditional Chinese medicine formula by HPLC fingerprinting combined with molecular docking.

Abstract

A traditional Chinese medicine formula (Fuzheng Yiliu decoction; FZYLD) has been used for many years in clinical settings to cure liver tumors; however, no empirical research has reported its chemical composition. In this paper, 21 chief constituents were distinguished from FZYLD using high-performance liquid chromatography-mass spectrometry fingerprint analysis. Molecular docking studies for B-cell lymphoma-extra large (Bcl-XL), interleukin (IL)-2, and tumor necrosis factor-α (TNF-α) were bound to evaluate their anticancer activities. 7 compounds showed potential Bcl-XL high affinity binding with a dissociate constant (Kd) < 10 μM; 7 compounds bound with IL-2 had a Kd < 10 μM; and 11 compounds showed potential TNF-α inhibition with a Kd < 10 μM. Moreover, 11 compounds showed better anticancer activity toward human HepG2 (hepatoma) cancer cell lines with IC50 values < 100 μM in vitro. The killings effects of natural killer cells can be activated by FZYLD on HepG2 cells and regulate the immune response through modulating IL-2 and TNF-α expression in vivo. In the "Fuzheng" Chinese medicine formula, many substances participate in the complex regulation of the immune network to execute the anti-tumor effect. The combination approach of chromatographic fingerprint and computer virtual docking used to explore active chemical matter of traditional Chinese medicine is extremely valuable.

• Authors: Liwu Chen, Jian Du, Qiwen Dai, Hongcheng Zhang, Wensheng Pang, Juan Hu
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 83 Pg. 294-306 (Aug 18 2014) ISSN: 1768-3254 [Electronic] France
• PMID: 24974349 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Drugs, Chinese Herbal
• Interleukin-2
• Saponins
• Triterpenes
• Tumor Necrosis Factor-alpha
• bcl-X Protein
• fuzheng yiliu
• astragaloside A
• Diosgenin

Topics

• Antineoplastic Agents (chemistry, metabolism, pharmacology)
• Cell Survival (drug effects)
• Chemistry, Pharmaceutical
• Chromatography, High Pressure Liquid
• Computational Biology
• Diosgenin (analysis)
• Drugs, Chinese Herbal (chemistry, metabolism, pharmacology)
• Hep G2 Cells
• Humans
• Interleukin-2 (chemistry, metabolism)
• Killer Cells, Natural (drug effects, immunology)
• Medicine, Chinese Traditional
• Molecular Docking Simulation
• Protein Conformation
• Saponins (analysis)
• Triterpenes (analysis)
• Tumor Necrosis Factor-alpha (chemistry, metabolism)
• bcl-X Protein (chemistry, metabolism)