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Article Publish Status: FREE
Abstract Title:

(-)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer.

Abstract Source:

Nutrients. 2020 Jun 11 ;12(6). Epub 2020 Jun 11. PMID: 32545325

Abstract Author(s):

Abu Bakar Siddique, Phillip C S R Kilgore, Afsana Tajmim, Sitanshu S Singh, Sharon A Meyer, Seetharama D Jois, Urska Cvek, Marjan Trutschl, Khalid A El Sayed

Article Affiliation:

Abu Bakar Siddique

Abstract:

Lung cancer (LC) represents the topmost mortality-causing cancer in the U.S. LC patients have overall poor survival rate with limited available treatment options. Dysregulation of the mesenchymal epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) initiates aggressive LC profile in a subset of patients. The Mediterranean extra-virgin olive oil (EVOO)-rich diet already documented to reduce multiple malignancies incidence. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid exclusively occurring in EVOO and showed documented anti-breast and other cancer activities via targeting c-MET. This study shows the novel ability of OC to suppress LC progression and metastasis through dual targeting of c-MET and COX-2. Western blot analysis and COX enzymatic assay showed significant reduction in the total and activated c-MET levels and inhibition of COX1/2 activity in the lung adenocarcinoma cells A549 and NCI-H322M, in vitro. In addition, OC treatment caused a dose-dependent inhibition of the HGF-induced LC cells migration. Daily oral treatment with 10 mg/kg OC for 8 weeks significantly suppressed the LC A549-Luc progression and prevented metastasis to brain and other organs in a nude mouse tail vein injection model. Further, microarray data of OC-treated lung tumors showed a distinct gene signature that confirmed the dual targeting of c-MET and COX2. Thus, the EVOO-based OC is an effective lead with translational potential for use as a prospective nutraceutical to control LC progression and metastasis.

Study Type : In Vitro Study

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