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Dz13, a c-jun DNAzyme, is a potent inducer of caspase-2 activation

Dass, Crispin R and Galloway, S and Choong, Peter F. M (2010) Dz13, a c-jun DNAzyme, is a potent inducer of caspase-2 activation. Oligonucleotides, 20 (3). pp. 137-146. ISSN 1545-4576

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Abstract

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.

Item Type: Article
Additional Information:

Online ISSN: 1557-8526

Uncontrolled Keywords: ResPubID21860. DNA, catalytic chemistry, C-JUN, Dz13, genetics, tumours, cancer, mice, Caspase-2
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1112 Oncology and Carcinogenesis
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
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Depositing User: VUIR
Date Deposited: 02 Feb 2012 05:25
Last Modified: 02 Feb 2012 05:25
URI: http://vuir.vu.edu.au/id/eprint/7565
DOI: 10.1089/oli.2009.0226
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Citations in Scopus: 9 - View on Scopus

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