• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    Phenformin and Oral Cancer: The Role of Organic Cation Transporters

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Irhama_umaryland_0373N_10657.pdf
    Size:
    1.088Mb
    Format:
    PDF
    Download
    Author
    Irhama, Hussein
    Advisor
    Schneider, Abraham
    Date
    2015
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Abstract: Background: Compelling preclinical evidence indicates that the biguanide metformin, the most widely prescribed oral antidiabetic drug in the United States, prevents the progression of oral premalignant lesions into oral squamous cell carcinoma (OSCC). Metformin triggers antitumoral responses in part by inhibiting the oncogenic mammalian target of rapamycin (mTOR) pathway through activation of one of its key negative regulators and critical sensor of cellular bioenergetics, the AMP-activated protein kinase (AMPK). As a small hydrophilic cationic compound, metformin enters cells through cell membrane organic cation transporters (OCTs) belonging to the SLC22A gene family. Emerging evidence also shows that OCT expression is significantly reduced or absent as OSCC tumors become more aggressive and less differentiated. Therefore, we hypothesized that phenformin, another biguanide compound with a more hydrophobic structure and possibly more potent antineoplastic activity, might exert its antitumoral effects through an OCT-independent manner. This hypothesis was tested through the following specific aims: (1) To determine whether phenformin induces OSCC growth inhibitory actions; (2) To determine whether OCT function is necessary for phenformin-induced activation of the AMPK signaling pathway. Methods and Materials: Cell viability assays and immunoblotting techniques were conducted by using human-derived OSCC cell lines HN6 and HN13. Results: Our results demonstrated that: (1) phenformin significantly reduced OSCC cell viability, and (2) phenformin appeared to activate AMPK signaling through an OCT-independent manner. Conclusion: This in vitro study shows that phenformin, in contrast to metformin, may exert a more potent antineoplastic effect since it decreased OSCC cell viability with much lower doses. In addition, phenformin appears not to be dependent on OCT expression and activity to activate AMPK signaling. Collectively, these studies suggest that phenformin might become an alternative biguanide, alone or in combination with conventional chemotherapy agents, when treating OCT-deficient OSCC tumors.
    Description
    University of Maryland, Baltimore. Biomedical Sciences. M.S. 2015
    Keyword
    Phenformin--pharmacokinetics
    Phenformin--therapeutic use
    Mouth Neoplasms--prevention & control
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/4844
    Collections
    Theses and Dissertations School of Dentistry
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.