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Open Access Highly Accessed Research article

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

Yunbao Pan13, Mengyao Wang1, Xianzhang Bu2, Yinglin Zuo2, Sumei Wang1, Dujuan Wang1, Qing Liu1, Bojin Su1, Tao Xu1, Chunhua Wang1, Francois X Claret34* and Huiling Yang1*

Author Affiliations

1 Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People’s Republic of China

2 Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, People's Republic of China

3 Department of Systems Biology, Unit 950, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

4 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

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BMC Cancer 2013, 13:323  doi:10.1186/1471-2407-13-323

Published: 1 July 2013

Abstract

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.

Keywords:
Nasopharyngeal carcinoma; Tumorigenesis; Epstein-Barr virus–associated malignancy; Jab1/CSN5; Curcumin