title: Anti-metastatic action of anacardic acid targets VEGF-induced signalling pathways in epithelial to mesenchymal transition.
abstract: Anacardic acid is a major constituent of nutshell of cashew. In this study, we have isolated it from the leaves of Anacardium Occidentale L. using polarity-based fractionation and confirmed the structure using GC-MS, NMR and FT-IR. The main focus of this study is to harness the molecular mechanism of anti-metastatic action of anacardic acid (A1). We have used MCF-7, a weak metastatic and U-87, a highly metastatic, breast and glioma cell lines respectively, for our study. We have shown that VEGF increases migration and invasion activities of MCF-7 cells, upon overexpression of Twist and Snail genes. It is observed from the current study that exposure of MCF-7 cells to A1 resulted in upregulation of epithelial marker E-cadherin with a concomitant decrease in the expression of mesenchymal markers Twist and Snail gene expression besides exhibiting a strong anti-migratory and anti-invasive activity. In metastatic U-87 glioma cells, treatment with A1 decreased the phosphorylation of MAP kinases, inhibited the translocation of Sp1 and down regulated VEGF and Flt-1 gene expression. Overall, the current findings demonstrate for the first time that anacardic acid functions as a potent EMT inhibitor by targeting VEGF signaling pathway, providing a novel template for drug discovery.
authors: Department of Studies in Biotechnology, University of Mysore.
authors: Puttananjaiah
authors: P
authors: Shilpa
authors: Keshavaiah
authors: K
authors: Kaveri
authors: Bharathi P
authors: BP
authors: Salimath
mesh_terms: D048729:Anacardic Acids / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D008401:Gas Chromatography-Mass Spectrometry; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009687:Nuclear Proteins / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D048729:Anacardic Acids; D020533:Angiogenesis Inhibitors; D009687:Nuclear Proteins; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1; D042461:Vascular Endothelial Growth Factor A; C088115:anacardic acid