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

Chih Ho Lai, Chia Shuo Chang, Hsin Ho Liu, Yuh Shyan Tsai, Feng Ming Hsu, Yung Luen Yu, Cheng Kuo Lai, Leah Gandee, Rey Chen Pong, Heng Wei Hsu, Lan Yu, Debabrata Saha, Jer Tsong Hsieh

Research output: Contribution to journalArticle

15 Scopus citations

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 languageEnglish (US)
Pages (from-to)5523-5534
Number of pages12
JournalOncotarget
Volume5
Issue number14
DOIs
StatePublished - 2014

Keywords

  • Cytolethal distending toxin
  • Ionizing radiation
  • Prostate cancer
  • Radio-resistance

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Lai, C. H., Chang, C. S., Liu, H. H., Tsai, Y. S., Hsu, F. M., Yu, Y. L., Lai, C. K., Gandee, L., Pong, R. C., Hsu, H. W., Yu, L., Saha, D., & Hsieh, J. T. (2014). Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin. Oncotarget, 5(14), 5523-5534. https://doi.org/10.18632/oncotarget.2133