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(−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer
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 su...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353354/ https://www.ncbi.nlm.nih.gov/pubmed/32545325 http://dx.doi.org/10.3390/nu12061749 |
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author | Siddique, Abu Bakar Kilgore, Phillip C.S.R. Tajmim, Afsana Singh, Sitanshu S. Meyer, Sharon A. Jois, Seetharama D. Cvek, Urska Trutschl, Marjan Sayed, Khalid A. El |
author_facet | Siddique, Abu Bakar Kilgore, Phillip C.S.R. Tajmim, Afsana Singh, Sitanshu S. Meyer, Sharon A. Jois, Seetharama D. Cvek, Urska Trutschl, Marjan Sayed, Khalid A. El |
author_sort | Siddique, Abu Bakar |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7353354 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73533542020-07-15 (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer Siddique, Abu Bakar Kilgore, Phillip C.S.R. Tajmim, Afsana Singh, Sitanshu S. Meyer, Sharon A. Jois, Seetharama D. Cvek, Urska Trutschl, Marjan Sayed, Khalid A. El Nutrients Article 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. MDPI 2020-06-11 /pmc/articles/PMC7353354/ /pubmed/32545325 http://dx.doi.org/10.3390/nu12061749 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Siddique, Abu Bakar Kilgore, Phillip C.S.R. Tajmim, Afsana Singh, Sitanshu S. Meyer, Sharon A. Jois, Seetharama D. Cvek, Urska Trutschl, Marjan Sayed, Khalid A. El (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title | (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title_full | (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title_fullStr | (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title_full_unstemmed | (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title_short | (−)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer |
title_sort | (−)-oleocanthal as a dual c-met-cox2 inhibitor for the control of lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353354/ https://www.ncbi.nlm.nih.gov/pubmed/32545325 http://dx.doi.org/10.3390/nu12061749 |
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