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    Involvement of Caspase-2 in Cisplatin-Induced Cell Death in 2008 Ovarian Cancer Cells

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    Date
    2008-04-01
    Author
    Adkins, Brett T.
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    Abstract
    Adkins, B., Involvement of caspase-2 in cisplatin-induced cell death in 2008 ovarian cancer cells. Master of Science (Molecular Biology and Immunology) April, 2008, 59 pp., 12 illustrations, bibliography, 73 titles. Cisplatin, one of the most effective anticancer drugs in the treatment of ovarian cancer, causes DNA damage and leads to apoptosis. Caspases, a family of cysteine proteases, are essential for the induction of apoptosis. Initiator caspases activate effector caspases to trigger apoptosis. Caspase-2 can function as both an initiator and effector caspase although there are controversies regarding its role in DNA damage-induced apoptosis. Caspase-2 is the only caspase constitutively located in the nucleus, although its function there is unknown. In the present study we have investigated if caspase-2 is important during cisplatin-induced apoptosis and whether cisplatin treatment affects the localization of caspase-2. Caspase-2 depletion suggested that caspase-2 acts upstream of caspase-2 acts upstream of caspase-9 in cisplatin-induced apoptosis. We also made a novel observation that rottlerin, an inhibitor of DNA damage-induced apoptosis, specifically downregulates caspase-2 via the ubiquitin proteamose-mediated pathway. We further show that cisplatin induces caspase-2 translocation out of the nucleus. Moreover, translocation of caspase-2 is more important for cisplatin-induced cell death.
    Subject
    Cancer Biology
    Cell Anatomy
    Cell and Developmental Biology
    Cell Biology
    Cells
    Cellular and Molecular Physiology
    Developmental Biology
    Genetics
    Genetics and Genomics
    Genomics
    Life Sciences
    Medical Cell Biology
    Medical Genetics
    Medicine and Health Sciences
    Microbiology
    Molecular Genetics
    Other Cell and Developmental Biology
    Other Genetics and Genomics
    Cell death
    ovarian cancer cells
    cisplatin-induced cell death
    capase-2
    cysteine proteases
    apoptosis
    DNA damage
    rottlerin
    translocation
    URI
    https://hdl.handle.net/20.500.12503/26347
    Collections
    • School of Biomedical Sciences
    • Theses and Dissertations

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