Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation
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, whi...
| Main Authors: | , , |
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| Format: | Journal Article |
| Published: |
Mary Ann Liebert inc
2010
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| Online Access: | http://hdl.handle.net/20.500.11937/23209 |
| _version_ | 1848751086791294976 |
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| author | Dass, Crispin Galloway, S. Choong, P. |
| author_facet | Dass, Crispin Galloway, S. Choong, P. |
| author_sort | Dass, Crispin |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T07:47:08Z |
| format | Journal Article |
| id | curtin-20.500.11937-23209 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:47:08Z |
| publishDate | 2010 |
| publisher | Mary Ann Liebert inc |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-232092017-09-13T13:57:03Z Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation Dass, Crispin Galloway, S. Choong, P. 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. 2010 Journal Article http://hdl.handle.net/20.500.11937/23209 10.1089/oli.2009.0226 Mary Ann Liebert inc restricted |
| spellingShingle | Dass, Crispin Galloway, S. Choong, P. Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title | Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title_full | Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title_fullStr | Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title_full_unstemmed | Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title_short | Dz13, a c-jun DNAzyme, Is a Potent Inducer of Caspase-2 Activation |
| title_sort | dz13, a c-jun dnazyme, is a potent inducer of caspase-2 activation |
| url | http://hdl.handle.net/20.500.11937/23209 |