title: 3-Deazaneplanocin A May Directly Target Putative Cancer Stem Cells in Biliary Tract Cancer.
abstract: OBJECTIVE
  Polycomb repressive complex 2 (PRC2), an epigenetic master regulator, contributes to progression and development of biliary tract cancer (BTC). The present study investigated the effects of the PRC2 inhibitor 3-deazaneplanocin A (DZNep) on BTC cell lines.
  
  
  METHODS
  In vitro effects of DZNep treatment were analyzed for cell viability, gene expression and functional characteristics of cancer stem cell (CSC).
  
  
  RESULTS
  DZNep treatment caused a cell line- and dose-dependent decrease in viability. In the EGI-1 cell line, a direct cytotoxic effect was accompanied by mRNA down-regulation of the PRC2 core components, cyclins as well as of CSC-related genes. Furthermore, DZNep affected putative CSCs by reduction of sphere formation and aldehyde dehydrogenase-1-positive cells. The stem cell characteristics of these subpopulations were verified by real-time polymerase chain reaction analysis.
  
  
  CONCLUSIONS
  Taken together, our results show that DZNep might be a promising pharmacological agent for future therapies regarding BTC.
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayr
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Andrej
authors.initials: A
authors.lastname: Wagner
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Stoecklinger
authors.affiliation: Laboratory for Functional and Molecular Membrane Physiology, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Jakab
authors.affiliation: Institute of Pathology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Illig
authors.affiliation: Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Frieder
authors.initials: F
authors.lastname: Berr
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.affiliation: Department of Visceral, Thoracic and Vascular Surgery, Philipps University of Marburg, Marburg, Germany.
authors.forename: Pietro
authors.initials: P
authors.lastname: Di Fazio
authors.affiliation: Institute for Surgical Research, Philipps University of Marburg, Marburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ocker
authors.affiliation: Institute of Pathology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University, Salzburg, Austria Laboratory for Tumour Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria t.kiesslich@salk.at.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001661:Biliary Tract Neoplasms / Q000235:genetics / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016213:Cyclins; D012333:RNA, Messenger; C048460:3-deazaneplanocin; D063151:Polycomb Repressive Complex 2; D000241:Adenosine
keywords: Biliary tract cancer; DZNep; EZH2; PRC2; anchorage-independent growth; cancer stem cells