Mangiferin fails to attenuate TGFß-induced EMT in Non-Small-Cell Lung Cancer

ORCiD

John C. Livesey: 0000-0001-9010-5970

Document Type

Poster

Conference Title/Conference Publication

Pacific Undergraduate Research & Creativity Conference

Organization

University of the Pacific

Location

Stockton, CA

Conference Dates

April 20-May 9, 2015

Date of Presentation

4-25-2015

Abstract

Non-Small Cell Lung Carcinomas are amongst the most drug resistant and metastatic cancers of epithelial origin. Understanding the processes behind drug resistance and metastasis is imperative in order to improve NSCLC patient survivability. A process called the epithelial-tomesenchymal transition (EMT) is suspected to underlie not only metastasis but also to effect large changes in tumor drug responsiveness. EMT involves a genetic overhaul that causes a cancer cell to break free of its tumor matrix and to become more motile and invasive. Our goal is to elucidate the role that the tumor microenvironment plays in modulating EMT in addition to screening chemical agents that may reverse (or slow down) this process. Recent studies have shown that Mangiferin, an antioxidant sourced from the bark of the Mangifera indica tree, may be effective in reversing the EMT process in breast and prostate cancers. Despite cancers of epithelial origin sharing highly conserved EMT pathways, they still differ considerably. Thus, a drug may be effective in one type of cancer but completely ineffective in another. Studies were conducted to evaluate if Mangiferin could reverse EMT in two NSCLC cell lines (A549 and H1299). EMT was induced through treatment of cells with Transforming Growth Factor Beta (TGF-ß). EMT was confirmed through microscopic observation and Western blotting for epithelial and mesenchymal markers (E-cadherin and vimentin, respectively). We found that Mangiferin was ineffective in reversing EMT and rescuing the epithelial phenotype. We also found that one of the NSCLC cell lines, A549, had genetically drifted and had become more mesenchymal in character.

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