title: Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin.
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.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chih-Ho
authors.initials: CH
authors.lastname: Lai
authors.affiliation: School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Shuo
authors.initials: CS
authors.lastname: Chang
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Hsin-Ho
authors.initials: HH
authors.lastname: Liu
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Department of Urology, Medical College and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yuh-Shyan
authors.initials: YS
authors.lastname: Tsai
authors.affiliation: Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Feng-Ming
authors.initials: FM
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Cheng-Kuo
authors.initials: CK
authors.lastname: Lai
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Leah
authors.initials: L
authors.lastname: Gandee
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Rey-Chen
authors.initials: RC
authors.lastname: Pong
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Heng-Wei
authors.initials: HW
authors.lastname: Hsu
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Debabrata
authors.initials: D
authors.lastname: Saha
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas, USA. Graduate Institute of Cancer Biology, China Medical University, Taichung, Taiwan.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001427:Bacterial Toxins / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics
chemical_list: D001427:Bacterial Toxins; C462952:DAB2IP protein, human; D011838:Radiation-Sensitizing Agents; C067044:cytolethal distending toxin; D020703:ras GTPase-Activating Proteins