title: Parthenolide inhibits cancer stem-like side population of nasopharyngeal carcinoma cells via suppression of the NF-κB/COX-2 pathway.
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.
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Liao
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xia
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China.
authors.forename: Qun-Ying
authors.initials: QY
authors.lastname: Zhuang
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Meng-Jun
authors.initials: MJ
authors.lastname: Hou
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Luo
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Gao
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Li
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Hui-Feng
authors.initials: HF
authors.lastname: Chen
authors.affiliation: 2. Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Ling
authors.affiliation: 1. State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen Fujian 361102, PR China.
authors.forename: Cheng-Yong
authors.initials: CY
authors.lastname: He
authors.affiliation: 3. Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, PR China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Zhong-Ning
authors.initials: ZN
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D012717:Sesquiterpenes / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D012717:Sesquiterpenes; C002669:parthenolide; D051546:Cyclooxygenase 2
keywords: cyclooxygenase-2; nasopharyngeal carcinoma; nuclear factor-kappa B; parthenolide; side population cells.