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Active-Italia: Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer

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

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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.

Conclusions – Oleocanthal, an exclusive olive-oil phenolic component, has captured an increasing interest as a potential anticancer lead. Collectively, the present study findings validate OC as a potential entity appropriate for use to control LC through its dual c-MET and COX2 modulation. Microarray data further confirmed the positive OC therapeutic potential against LC at the gene levels, validating its c-MET/COX2 suppressive effects, along with the suppression of downstream network of genes associated with LC proliferation, migration and metastasis.

Source of the Article

Abu Bakar Siddique, Phillip C.S.R. Kilgore, […], and Khalid A. El Sayed

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