TexasScholarWorks
    • Login
    • Submit
    View Item 
    •   Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    • Repository Home
    • UT Electronic Theses and Dissertations
    • UT Electronic Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Investigation of the effects of alpha-TEA, MSA and t-RES alone and in combination on human MDA-MB-435 breast cancer cells in vitro and in vivo

    Thumbnail
    View/Open
    snyderr78858.pdf (4.234Mb)
    Date
    2006
    Author
    Snyder, Rachel Marie
    Share
     Facebook
     Twitter
     LinkedIn
    Metadata
    Show full item record
    Abstract
    Cancer is the leading cause of death in U.S. women under 85. It is becoming increasingly clear that individual treatments will not cure cancer and that combination approaches may be more effective. Our goal was to further understand the molecular mechanisms of α-TEA's anticancer effects, and to explore its potential in combination with two other agents, MSC/MSA and t-RES. Data support the efficacy of α-TEA as a chemopreventive and chemotherapeutic agent in human breast cancer cells. We first determined that α-TEA, t-RES, and MSC/MSA inhibit cell proliferation, induce differentiation, and synergize when used in combination to induce apoptosis. Treatment enhanced cell death was seen in other cancer cell lines and no cell killing was seen in HMECs. Next, the ability of these agents to reduce tumor burden, induce apoptosis, and prevent proliferation of MDA-MB-435-F-L cells was investigated in vivo. α-TEA and low doses of t-RES reduce tumor burden in athymic nude mice but combinations of the three compounds were not as effective as α-TEA or t-RES alone. The three treatments significantly reduced visible and micrometastatic tumor foci. We showed that the efficacy of t-RES administered at low (10 mg/kg bw) and high (100 mg/kg bw) concentrations was diet-related. Our third aim was to determine if these compounds could effectively inhibit the formation of DMBA and MNU-induced lesions in the MMOC and rat mammary carcinogenesis models. Each compound inhibited cancer lesions in these models but α-TEA and t-RES were better than MSA, and a combination of α-TEA and t-RES was best. Next, we examined apoptotic and survival signaling events that could lead to synergy after α-TEA and t-RES treatment. Pre-treatment sensitized the cancer cells to cell membrane receptor-mediated apoptosis. α-TEA and cotreatment induced cell death was caspases-dependent while that for t-RES was not. Next, decreases in prosurvival survivin and c-FLIP proteins were shown to be significant to treatment induced apoptosis. Based on the results reported here, we propose a signaling model where the synergy between α-TEA and t-RES is due to a combination of apoptosis and caspase-independent cell death (CICD).
    Department
    Institute for Cellular and Molecular Biology
    Description
    text
    URI
    http://hdl.handle.net/2152/2932
    Collections
    • UT Electronic Theses and Dissertations

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin

     

     

    Browse

    Entire RepositoryCommunities & CollectionsDate IssuedAuthorsTitlesSubjectsDepartmentsThis CollectionDate IssuedAuthorsTitlesSubjectsDepartments

    My Account

    Login

    Statistics

    View Usage Statistics

    Information

    About Contact Policies Getting Started Glossary Help FAQs

    University of Texas at Austin Libraries
    • facebook
    • twitter
    • instagram
    • youtube
    • CONTACT US
    • MAPS & DIRECTIONS
    • JOB OPPORTUNITIES
    • UT Austin Home
    • Emergency Information
    • Site Policies
    • Web Accessibility Policy
    • Web Privacy Policy
    • Adobe Reader
    Subscribe to our NewsletterGive to the Libraries

    © The University of Texas at Austin