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

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 downregula...

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Autores principales: Lai, Chih-Ho, Chang, Chia-Shuo, Liu, Hsin-Ho, Tsai, Yuh-Shyan, Hsu, Feng-Ming, Yu, Yung-Luen, Lai, Cheng-Kuo, Gandee, Leah, Pong, Rey-Chen, Hsu, Heng-Wei, Yu, Lan, Saha, Debabrata, Hsieh, Jer-Tsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170639/
https://www.ncbi.nlm.nih.gov/pubmed/25015118
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author Lai, Chih-Ho
Chang, Chia-Shuo
Liu, Hsin-Ho
Tsai, Yuh-Shyan
Hsu, Feng-Ming
Yu, Yung-Luen
Lai, Cheng-Kuo
Gandee, Leah
Pong, Rey-Chen
Hsu, Heng-Wei
Yu, Lan
Saha, Debabrata
Hsieh, Jer-Tsong
author_facet Lai, Chih-Ho
Chang, Chia-Shuo
Liu, Hsin-Ho
Tsai, Yuh-Shyan
Hsu, Feng-Ming
Yu, Yung-Luen
Lai, Cheng-Kuo
Gandee, Leah
Pong, Rey-Chen
Hsu, Heng-Wei
Yu, Lan
Saha, Debabrata
Hsieh, Jer-Tsong
author_sort Lai, Chih-Ho
collection PubMed
description 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.
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spelling pubmed-41706392014-09-22 Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin Lai, Chih-Ho Chang, Chia-Shuo Liu, Hsin-Ho Tsai, Yuh-Shyan Hsu, Feng-Ming Yu, Yung-Luen Lai, Cheng-Kuo Gandee, Leah Pong, Rey-Chen Hsu, Heng-Wei Yu, Lan Saha, Debabrata Hsieh, Jer-Tsong Oncotarget Research Paper 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. Impact Journals LLC 2014-06-26 /pmc/articles/PMC4170639/ /pubmed/25015118 Text en Copyright: © 2014 Lai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Lai, Chih-Ho
Chang, Chia-Shuo
Liu, Hsin-Ho
Tsai, Yuh-Shyan
Hsu, Feng-Ming
Yu, Yung-Luen
Lai, Cheng-Kuo
Gandee, Leah
Pong, Rey-Chen
Hsu, Heng-Wei
Yu, Lan
Saha, Debabrata
Hsieh, Jer-Tsong
Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title_full Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title_fullStr Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title_full_unstemmed Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title_short Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
title_sort sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170639/
https://www.ncbi.nlm.nih.gov/pubmed/25015118
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