(-)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer
NUTRIENTS
Authors: Siddique, Abu Bakar; Kilgore, Phillip C. S. R.; Tajmim, Afsana; Singh, Sitanshu S.; Meyer, Sharon A.; Jois, Seetharama D.; Cvek, Urska; Trutschl, Marjan; El Sayed, Khalid A.
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.
Characterization of cytokine profile to distinguish latent tuberculosis from active tuberculosis and healthy controls
CYTOKINE
Authors: He, Jianqin; Fan, Yumei; Shen, Dongni; Yu, Mengjia; Shi, Lingfang; Ding, Shiping; Li, Lanjuan
Abstract
Background: Tuberculosis (TB) is an infectious disease and its mortality rate ranks first. Latent tuberculosis infection (LTBI) means that a patient is infected with Mycobacterium tuberculosis, but has no relative clinical symptoms. It has been estimated that approximately 10% of patients with LTBI would develop into active tuberculosis. Therefore, it was urgent to search for more efficient biomarkers to discriminate LTBI from healthy population. Methods: The Luminex assay was employed to detect the quantity of cytokines secreted by mononuclear cells from peripheral blood stimulated with the ESAT6 protein among TB, LTBI and healthy controls. The cytokine profile was analyzed by principal components analysis and the receiver operating characteristic curve analysis. Results: The principal components analysis indicated that LTBI and TB were clearly separated from healthy controls, and that LTBI was also successfully differentiated from healthy controls. The cytokine profiling method to distinguish LTBI from healthy controls has a sensitivity and specificity of 100%. Nine potential biomarkers, including IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-15, IL-22 and IL-18, were identified, and these cytokines were considered as a potential cytokine complex for more effectively discriminating LTBI from healthy controls. Conclusion: IL-23, IL-21, HGF, Bngf, IL-27, IL-31, IL-1 beta, IL-22 and IL-18 were demonstrated to be the potential cytokine complex for the assessment between LTBI and healthy controls.