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Open Access Highly Accessed Research article

Evaluation of a curcumin analog as an anti-cancer agent inducing ER stress-mediated apoptosis in non-small cell lung cancer cells

Zhiguo Liu1, Yusheng Sun2, Luqing Ren1, Yi Huang1, Yuepiao Cai1, Qiaoyou Weng1, Xueqian Shen1, Xiaokun Li1, Guang Liang1* and Yi Wang1*

Author Affiliations

1 Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, 325035 Wenzhou, Zhejiang, China

2 Department of general surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China

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BMC Cancer 2013, 13:494  doi:10.1186/1471-2407-13-494

Published: 24 October 2013

Abstract

Background

Recent advances have highlighted the importance of the endoplasmic reticulum (ER) in cell death processes. Pharmacological interventions that effectively enhance tumor cell death through activating ER stress have attracted a great deal of attention for anti-cancer therapy.

Methods

A bio-evaluation on 113 curcumin analogs against four cancer cell lines was performed through MTT assay. Furthermore, real time cell assay and flow cytometer were used to evaluate the apoptotic induction of (1E,4E)-1,5-bis(5-bromo-2-ethoxyphenyl)penta-1,4-dien-3-one (B82). Western blot, RT-qPCR, and siRNA were then utilized to confirm whether B82-induced apoptosis is mediated through activating ER stress pathway. Finally, the in vivo anti-tumor effect of B82 was evaluated.

Results

B82 exhibited strong anti-tumor activity in non-small cell lung cancer (NSCLC) H460 cells. Treatment with B82 significantly induced apoptosis in H460 cells in vitro and inhibited H460 tumor growth in vivo. Further studies demonstrated that the B82-induced apoptosis is mediated by activating ER stress both in vitro and in vivo.

Conclusions

A new monocarbonyl analog of curcumin, B82, exhibited anti-tumor effects on H460 cells via an ER stress-mediated mechanism. B82 could be further explored as a potential anticancer agent for the treatment of NSCLC.

Keywords:
Curcumin analogs; Anti-cancer; ER stress; Non-small cell lung cancer; CHOP