title: Cyclopamine decreased the expression of Sonic Hedgehog and its downstream genes in colon cancer stem cells.
abstract: Backround: Most solid cancers including colon cancer are believed to be initiated from and maintained by cancer stem cells (CSCs), that are responsible for treatment resistance, resulting in tumor relapse. The aim of this study was to clarify the possible role of the Sonic Hedgehog (Shh) signaling pathway in the regulation of cancer stem cells.
  
  
  METHODS
  The HCT-116 cell line was cultured with fetal bovine serum in RPMI-1640 medium and its sphere was grown in serum-free non-adherent culture. Gene expressions were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) from cells treated with and without cyclopamine.
  
  
  RESULTS
  HCT-116 sphere-derived cells grown in serum-free, non-adherent culture, showed significantly increased expression of stem cell markers, Shh downstream genes and epithelial-mesenchymal transition (EMT) markers compared to parental cells grown in conventional culture. The expression of stemness markers, Shh downstream genes and EMT markers were higher in cancer spheres than the parental cell line and down-regulated by cyclopamine treatment in a dose-dependent manner.
  
  
  CONCLUSIONS
  Overall, these findings show that cyclopamine treatment could down-regulate the expression of stemness markers, shh downstream genes and EMT markers on HCT-116 spheres.
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Bat-Erdene
authors.initials: BE
authors.lastname: Batsaikhan
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan yoshikawa.kozo@tokushima-u.ac.jp.
authors.forename: Kozo
authors.initials: K
authors.lastname: Yoshikawa
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kurita
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Takasu
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kashihara
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D062725:Tight Junction Proteins / Q000235:genetics; D019108:Tight Junctions / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D053823:Hedgehog Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D062725:Tight Junction Proteins; D014704:Veratrum Alkaloids; C000541:cyclopamine
keywords: Cancer stem-like cells; cancer cells; epithelial-mesenchymal transition; sonic hedgehog