Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin

Lai CH, Chang CS, Liu HH, Tsai YS, Hsu FM, Yu YL, Lai CK, Gandee L, Pong RC, Hsu HW, Yu L, Saha D, Hsieh JT.
Source: OncoTarget
Publication Date: (2014)
Issue: 5(14): 5523-34
Research Area:
Cancer Research/Cell Biology
Basic Research
Cells used in publication:
Species: human
Tissue Origin: prostate
Cytolethal distending toxin (CDT) produced by Campylobacter jejuni is a genotoxin that induces cell-cycle arrest and apoptosis in mammaliancells. 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 andradiotherapy 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 thatCDT can be a potent therapeutic agent for radio-resistant PCa.