Theranostics 2015; 5(3):302-321. doi:10.7150/thno.8387

Research Paper

Parthenolide Inhibits Cancer Stem-Like Side Population of Nasopharyngeal Carcinoma Cells via Suppression of the NF-κB/COX-2 Pathway

Kun Liao2*, Bin Xia2*, Qun-Ying Zhuang1, Meng-Jun Hou2, Yu-Jing Zhang2, Bing Luo1, Yang Qiu1, Yan-Fang Gao2, Xiao-Jie Li2, Hui-Feng Chen2, Wen-Hua Ling2, Cheng-Yong He1, Yi-Jun Huang3, Yu-Chun Lin 1,2✉, Zhong-Ning Lin1,2✉

1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China.
2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
3. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
*These authors contributed equally to this work.

Abstract

Cancer stem cells play a central role in the pathogenesis of nasopharyngeal carcinoma and contribute to both disease initiation and relapse. In this study, cyclooxygenase-2 (COX-2) was found to regulate cancer stem-like side population cells of nasopharyngeal carcinoma cells and enhance cancer stem-like cells' characteristics such as higher colony formation efficiency and overexpression of stemness-associated genes. The regulatory effect of COX-2 on cancer stem-like characteristics may be mediated by ABCG2. COX-2 overexpression by a gain-of-function experiment increased the proportion of side population cells and their cancer stemness properties. The present study also demonstrated that in contrast to the classical chemotherapy drug 5-fluorouracil, which increased the proportion of side population cells and upregulated the expression of COX-2, parthenolide, a naturally occurring small molecule, preferentially targeted the side population cells of nasopharyngeal carcinoma cells and downregulated COX-2. Moreover, we found that the cancer stem-like cells' phenotype was suppressed by using COX-2 inhibitors NS-398 and CAY10404 or knocking down COX-2 with siRNA and shRNA. These findings suggest that COX-2 inhibition is the mechanism by which parthenolide induces cell death in the cancer stem-like cells of nasopharyngeal carcinoma. In addition, parthenolide exhibited an inhibitory effect on nuclear factor-kappa B (NF-κB) nucler translocation by suppressing both the phosphorylation of IκB kinase complex and IκBα degradation. Taken together, these results suggest that parthenolide may exert its cancer stem cell-targeted chemotherapy through the NF-κB/COX-2 pathway.

Keywords: parthenolide, nasopharyngeal carcinoma, cyclooxygenase-2, nuclear factor-kappa B, side population cells.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Liao K, Xia B, Zhuang QY, Hou MJ, Zhang YJ, Luo B, Qiu Y, Gao YF, Li XJ, Chen HF, Ling WH, He CY, Huang YJ, Lin YC, Lin ZN. Parthenolide Inhibits Cancer Stem-Like Side Population of Nasopharyngeal Carcinoma Cells via Suppression of the NF-κB/COX-2 Pathway. Theranostics 2015; 5(3):302-321. doi:10.7150/thno.8387. Available from http://www.thno.org/v05p0302.htm