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

作者：Dhanjal Jaspreet Kaur; Nigam Nupur; Sharma Sudhanshu; Chaudhary Anupama; Kaul Sunil C; Grover Abhinav^*; Wadhwa Renu

来源：BMC Cancer, 2014, 14(1): 775.

DOI：10.1186/1471-2407-14-775

• Embelin
• Breast cancer cells
• TACE inhibition
• MMP inactivation
• Anticancer

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-alpha). TNF-alpha 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-alpha. The latter is synthesized as a membrane anchored protein (pro-TNF-alpha); the soluble component of pro-TNF-alpha is then released into the extracellular space by the action of a protease called TNF-alpha 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.

• 出版日期2014-10-22