Curcumin analogue T83 exhibits potent antitumor activity and induces radiosensitivity through inactivation of Jab1 in nasopharyngeal carcinoma

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• 作者：Yunbao Pan (6) (7)
  Mengyao Wang (7)
  Xianzhang Bu (5)
  Yinglin Zuo (5)
  Sumei Wang (7)
  Dujuan Wang (7)
  Qing Liu (7)
  Bojin Su (7)
  Tao Xu (7)
  Chunhua Wang (7)
  Francois X Claret (6) (7)
  Huiling Yang (7)
  
• 关键词：Nasopharyngeal carcinoma ; Tumorigenesis ; Epstein ; Barr virus–associated malignancy ; Jab1/CSN5 ; Curcumin
• 刊名：BMC Cancer
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：13
• 期：1
• 全文大小：860KB
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  26. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/13/323/prepub
  
• 作者单位：Yunbao Pan (6) (7)
  Mengyao Wang (7)
  Xianzhang Bu (5)
  Yinglin Zuo (5)
  Sumei Wang (7)
  Dujuan Wang (7)
  Qing Liu (7)
  Bojin Su (7)
  Tao Xu (7)
  Chunhua Wang (7)
  Francois X Claret (6) (7)
  Huiling Yang (7)
  
  6. Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
  7. Experimental Therapeutic Academic Program and Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, 6767 Bertner Ave, Houston, TX, 77030, USA
  5. Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People’s Republic of China
  
• ISSN：1471-2407

文摘

Background Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus–associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC. Methods NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting. Results A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy. Conclusion Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC.