Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma

BMC Complementary and Alternative Medicine

Research Article

Qing Su¹  Xiang Kong²  Yan Zhang³  Ming-zhe Weng⁴  Zhi-wei Quan⁴  Wei Gong⁴  Ming-zhe Ma⁴  Jun-xiu Zhang⁵  Jie-ren Yang⁵  Li-qun Guo⁵  Guo-dong Wang⁶ 

[1] Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 200092, Shanghai, China;Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 200092, Shanghai, China;Department of Pharmacology, Wannan Medical College, 241002, Wuhu, Anhui, China;Department of Gastroenterology, Yijishan Hospital Affiliated to Wannan Medical College, 241001, Wuhu, Anhui, China;Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 200092, Shanghai, China;Department of Pharmacology, Wannan Medical College, 241002, Wuhu, Anhui, China;Department of Pharmacy, Wannan Medical College, 241002, Wuhu, Anhui, China;

关键词: Side Population;    Biliary Tract Cancer;    Side Population Cell;    Epithelial Differentiation;    Differentiate Condition;   

DOI  :  10.1186/1472-6882-14-254

 received in 2013-10-23, accepted in 2014-07-15,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundRecent studies have demonstrated that side population (SP) cells isolated from various cancer cell lines and primary tumors possess stem cell-like properties. Sesamin, a food-derived agent, possesses anti-cancer activities both in vitro and in vivo. The present study was designed to determine whether sesamin also have effects on cancer stem-like SP cells from gallbladder cancer (GBC).MethodsIn this study, we sorted SP cells by flow cytometry. SP cells were cultured and treated with sesamin. Tumor-sphere formation, colony formation, Matrigel invasion and tumorigenic potential were determined. Expression of nuclear NF-κB, IL-6, p-Stat3, Twist, E-cadherin and Vimentin was measured by Western blot, immunofluorescence staining or RT-PCR analysis. Nuclear NF-κB activity and IL-6 protein level were assessed with ELISA. Xenograft tumors were generated in nude mice.ResultsAfter treated with sesamin, SP cells differentiated into cells expressing the epithelial marker (E-cadherin). Sesamin effectively affected SP cells stem cell-like characteristics (i.e., tumor-sphere formation, colony-formation, Matrigel invasion), weakened the drug-resistance of SP cells and inhibited tumor growth both in vitro and in vivo. Treatment with sesamin significantly reduced the expression of nuclear NF-κB, IL-6, p-Stat3, Twist and Vimentin (a mesenchymal marker) in SP cells. Nuclear NF-κB activity and IL-6 level were also decreased after treatment with sesamin.ConclusionFood-derived sesamin directs the epithelial differentiation of cancer stem-like SP cells from GBC, which is associated with attenuation of NF-κB-IL-6-Stat3-Twist signal pathway.

【 授权许可】

Unknown   
© Kong et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.