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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

BMC Cancer. 2014 Oct 22 ;14:775. Epub 2014 Oct 22. PMID: 25336399

Abstract Author(s):

Jaspreet Kaur Dhanjal, Nupur Nigam, Sudhanshu Sharma, Anupama Chaudhary, Sunil C Kaul, Abhinav Grover, Renu Wadhwa

Article Affiliation:

Jaspreet Kaur Dhanjal

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.

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