{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T19:53:27Z","timestamp":1787601207083,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2020,6,11]],"date-time":"2020-06-11T00:00:00Z","timestamp":1591833600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006952","name":"Louisiana Board of Regents","doi-asserted-by":"publisher","award":["LEQSF (2017-20)-RD-B-07)"],"award-info":[{"award-number":["LEQSF (2017-20)-RD-B-07)"]}],"id":[{"id":"10.13039\/100006952","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014517","name":"Louisiana Biomedical Research Network","doi-asserted-by":"publisher","award":["8P20GM10342"],"award-info":[{"award-number":["8P20GM10342"]}],"id":[{"id":"10.13039\/100014517","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Segue Therapeutics, Shreveport, Louisiana","award":["ITRS-Matching"],"award-info":[{"award-number":["ITRS-Matching"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/nu12061749","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T05:02:24Z","timestamp":1591938144000},"page":"1749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["(\u2212)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-9475","authenticated-orcid":false,"given":"Abu Bakar","family":"Siddique","sequence":"first","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip C.S.R.","family":"Kilgore","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Louisiana State University Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-1141","authenticated-orcid":false,"given":"Afsana","family":"Tajmim","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3141-0224","authenticated-orcid":false,"given":"Sitanshu S.","family":"Singh","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon A.","family":"Meyer","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seetharama D.","family":"Jois","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Urska","family":"Cvek","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Louisiana State University Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Trutschl","sequence":"additional","affiliation":[{"name":"Department of Computer Science, Louisiana State University Shreveport, Shreveport, LA 71115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1456-4064","authenticated-orcid":false,"given":"Khalid A. El","family":"Sayed","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, 1800 Bienville Drive, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21590","article-title":"Cancer statistics, 2020","volume":"70","author":"Siegel","year":"2020","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Markham, M.J., Wachter, K., Agarwal, N., Bertagnolli, M.M., Chang, S.M., Dale, W., Diefenbach, C.S.M., Rodriguez-Galindo, C., George, D.J., and Gilligan, T.D. (2020). Clinical cancer advances 2020: Annual report on progress against cancer from the American Society of Clinical Oncology. J. Clin. 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