title: Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma.
abstract: BACKGROUND
  Recent 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).
  
  
  METHODS
  In 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.
  
  
  RESULTS
  After 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.
  
  
  CONCLUSIONS
  Food-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.
authors.forename: Xiang
authors.initials: X
authors.lastname: Kong
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming-zhe
authors.initials: MZ
authors.lastname: Weng
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Li-qun
authors.initials: LQ
authors.lastname: Guo
authors.forename: Jun-xiu
authors.initials: JX
authors.lastname: Zhang
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China. suqingxinhua@163.com.
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Quan
authors.forename: Jie-ren
authors.initials: JR
authors.lastname: Yang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004149:Dioxoles / Q000494:pharmacology*; D005260:Female; D005706:Gallbladder Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058985:Side-Population Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D015820:Cadherins; D004149:Dioxoles; D015850:Interleukin-6; D017705:Lignans; D016328:NF-kappa B; C054125:sesamin