ANTICANCER MECHANISM OF TOLFENAMIC ACID IN COLORECTAL CANCER

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dc.contributor.advisorLee, Seong-Hoen_US
dc.contributor.authorLou, Zhiyuanen_US
dc.contributor.departmentNutritionen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2016-06-22T05:50:13Z
dc.date.available2016-06-22T05:50:13Z
dc.date.issued2016en_US
dc.description.abstractColorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Chemopreventive therapies could be effective way to treat CRC. Tolfenamic acid, one of the NSAIDs, shows anti-cancer activities in several types of cancer. Aberrant Wnt/β-catenin regulation pathway is a major mechanism of colon tumorigenesis. Here, we sought to better define the mechanism by which tolfenamic acid suppresses colorectal tumorigenesis focusing on regulation of β-catenin pathway. Treatment of tolfenamic acid led to a down-regulation of β-catenin expression in dose dependent manner in human colon cancer cell lines without changing mRNA. MG132 inhibited tolfenamic acid-induced downregulation of β-catenin and exogenously overexpression β-catenin was stabilized in the presence of tolfenamic acid. Tolfenamic acid induced an ubiquitin-mediated proteasomal degradation of β-catenin. In addition, tolfenamic acid treatment decreased transcriptional activity of β-catenin and expression of Smad2 and Smad3 while overexpression of Smad 2 inhibited tolfenamic acid-stimulated transcriptional activity of β-catenin. Moreover, tolfenamic acid decreased β-catenin target gene such as vascular endothelial growth factor (VEGF) and cyclin D1. In summary, tolfenamic acid is a promising therapeutic drug targeting Smad 2-mediated downregulation of β-catenin in CRC.en_US
dc.identifierhttps://doi.org/10.13016/M2TJ5H
dc.identifier.urihttp://hdl.handle.net/1903/18231
dc.language.isoenen_US
dc.subject.pqcontrolledBiologyen_US
dc.subject.pqcontrolledNutritionen_US
dc.subject.pqcontrolledCellular biologyen_US
dc.subject.pquncontrolledanticancer activitiesen_US
dc.subject.pquncontrolledbeta-cateninen_US
dc.subject.pquncontrolledColon canceren_US
dc.subject.pquncontrolledTolfenamic aciden_US
dc.titleANTICANCER MECHANISM OF TOLFENAMIC ACID IN COLORECTAL CANCERen_US
dc.typeThesisen_US

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