Abstract
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni is a genotoxin that induces cell-cycle arrest and apoptosis in mammalian cells. Recent studies have demonstrated that prostate cancer (PCa) cells can acquire radio-resistance when DOC-2/DAB2 interactive protein (DAB2IP) is downregulated. In this study, we showed that CDT could induce cell death in DAB2IP-deficient PCa cells. A combination of CDT and radiotherapy significantly elicited cell death in DAB2IP-deficient PCa cells by inhibiting the repair of ionizing radiation (IR)-induced DNA double-strand break (DSB) during G2/M arrest, which is triggered by ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses. We also found that CDT administration significantly increased the efficacy of radiotherapy in a xenograft mouse model. These results indicate that CDT can be a potent therapeutic agent for radio-resistant PCa.
Original language | English (US) |
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Pages (from-to) | 5523-5534 |
Number of pages | 12 |
Journal | Oncotarget |
Volume | 5 |
Issue number | 14 |
DOIs | |
State | Published - 2014 |
Keywords
- Cytolethal distending toxin
- Ionizing radiation
- Prostate cancer
- Radio-resistance
ASJC Scopus subject areas
- Oncology