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dc.contributor.authorDass, Crispin
dc.contributor.authorGalloway, S.
dc.contributor.authorChoong, P.
dc.identifier.citationDass, C. and Galloway, S. and Choong, P. 2010. Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation. Oligonucleotides. 20 (3): pp. 137-147.

Signaling pathways for caspase-2-mediated apoptosis are poorly defined. This is partially due to a lack of a reproducible stimulus to trigger caspase-2 activation. We present the oligonucleotide Dz13, a DNA enzyme that cleaves c-Jun mRNA and is capable of inhibiting various model tumors in mice, which potently induces caspase-2 resulting in apoptosis in a panel of tumor cell lines. Dz13-mediated cell death occurred even in the absence of known caspase-2 molecular partners in p53-induced protein with a death domain, RIP-associated Ich-1/CED homologous protein with death domain, or DNA-dependent protein kinase catalytic subunit, or other caspases in cell lines of breast cancer, prostate cancer, osteosarcoma, and liposarcoma. z-VDVAD-fmk, caspase-2-/- mouse embryonic fibroblasts and siRNA silencing of caspase-2 in tumor cells abrogated Dz13-mediated cell death. In an orthotopic tumor model, expression of caspase-2 increased as the tumor metastasized and caspase-2 expression was sporadic in patient tumor specimens. These findings provide hope that Dz13, and other agents that evoke activation of caspase-2, may be therapeutic clinically.

dc.publisherMary Ann Liebert inc
dc.titleDz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation
dc.typeJournal Article
curtin.accessStatusFulltext not available

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