Cytolethal Distending Toxin Enhances Radiosensitivity in Prostate Cancer Cells by Regulating Autophagy

Frontiers in Cellular and Infection Microbiology

Kao, Min-Chuan¹  Chiang-Ni, Chuan³  Huang, Mei-Zi³  Lin, Ho⁴  Lai, Cheng-Kuo⁴  Lin, Chun-Jung⁴  Jiang, Zhi-Pei⁴  Chen, Yu-An⁵  Lo, U-Ging⁶  Chiu, Cheng-Hsun⁷  Hsieh, Jer-Tsong⁷  Lai, Chih-Ho⁷  Lin, Hwai-Jeng⁸  Liu, Hsin-Ho⁹  Lin, Chia-Der^1,10  Lin, Li-Chiung^1,11 

[1] Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan;Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan;Department of Medical Research, School of Medicine, Graduate Institute of Basic Medical Sciences, China Medical University and Hospital, Taichung, Taiwan;Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan;Department of Otolaryngology-Head and Neck Surgery, China Medical University and Hospital, Taichung, Taiwan;Department of Pediatrics, Molecular Infectious Disease Research Center, Chang Gung Children'Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, United States;Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang-Ho Hospital, New Taipei, Taiwan;Division of Urology, Department of Surgery, Taichung Tzu Chi General Hospital, Taichung, Taiwan;s Hospital and Chang Gung Memorial Hospital, Taoyuan, Taiwan

关键词: Campylobacter jejuni;    cytolethal distending toxin;    Cell Cycle;    Autophagy;    radioresistance;   

DOI  :  10.3389/fcimb.2017.00223

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Among these three toxin subunits, CdtB is the toxic moiety of CDT with DNase I activity, resulting in DNA double-strand breaks (DSB) and, consequently, cell cycle arrest at the G2/M stage and apoptosis. Radiation therapy is an effective modality for the treatment of localized prostate cancer (PCa). However, patients often develop radioresistance. Owing to its particular biochemical properties, we previously employed CdtB as a therapeutic agent for sensitizing radioresistant PCa cells to ionizing radiation (IR). In this study, we further demonstrated that CDT suppresses the IR-induced autophagy pathway in PCa cells by attenuating c-Myc expression and therefore sensitizes PCa cells to radiation. We further showed that CDT prevents the formation of autophagosomes via decreased high-mobility group box 1 (HMGB1) expression and the inhibition of acidic vesicular organelle (AVO) formation, which are associated with enhanced radiosensitivity in PCa cells. The results of this study reveal the detailed mechanism of CDT for the treatment of radioresistant PCa.

【 授权许可】

CC BY