Embelin inhibits TNF-α converting enzyme and cancer cell metastasis: molecular dynamics and experimental evidence.

Abstract

BACKGROUND:

Embelin, a quinone derivative, is found in the fruits of Embelia ribes Burm (Myrsinaceae). It has been shown to have a variety of therapeutic potentials including anthelmintic, anti-tumor, anti-diabetic, anti-bacterial and anti-inflammation. Inflammation is an immunological response to external harmful stimuli and is regulated by an endogenous pyrogen and pleiotropic pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α). TNF-α production has been implicated in a variety of other human pathologies including neurodegeneration and cancer. Several studies have shown that the anti-inflammatory activity of embelin is mediated by reduction in TNF-α. The latter is synthesized as a membrane anchored protein (pro-TNF-α); the soluble component of pro-TNF-α is then released into the extracellular space by the action of a protease called TNF-α converting enzyme (TACE). TACE, hence, has been proposed as a therapeutic target for inflammation and cancer.

METHODS:

We used molecular docking and experimental approaches to investigate the docking potential and molecular effects of embelin to TACE and human cancer cell characteristics, respectively.

RESULTS:

We demonstrate that embelin is a potential inhibitor of TACE. Furthermore, in vitro studies revealed that it inhibits malignant properties of cancer cells through inactivation of metastatic signaling molecules including MMPs, VEGF and hnRNP-K in breast cancer cells.

CONCLUSION:

Based on the molecular dynamics and experimental data, embelin is proposed as a natural anti-inflammatory and anticancer drug.

• Authors: Jaspreet Kaur Dhanjal, Nupur Nigam, Sudhanshu Sharma, Anupama Chaudhary, Sunil C Kaul, Abhinav Grover, Renu Wadhwa
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 775 (Oct 22 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25336399 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzoquinones
• Ligands
• ADAM Proteins
• ADAM17 Protein
• ADAM17 protein, human
• embelin

Topics

• ADAM Proteins (antagonists & inhibitors, chemistry)
• ADAM17 Protein
• Benzoquinones (chemistry, pharmacology)
• Catalytic Domain
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Humans
• Ligands
• Models, Molecular
• Molecular Conformation
• Molecular Docking Simulation
• Molecular Dynamics Simulation
• Neoplasm Metastasis
• Neoplasms (drug therapy, metabolism, pathology)
• Protein Binding
• Tumor Stem Cell Assay