title: Propranolol inhibits growth of hemangioma-initiating cells but does not induce apoptosis.
abstract: BACKGROUND
  Infantile hemangioma (IH) is the most common tumor of infancy. The first-line therapy for IH is propranolol, a nonselective β-adrenergic receptor antagonist. However, mechanisms for the therapeutic effect of propranolol and regrowth of IH following cessation of treatment in some cases are not clear. We have recently shown that IH arises from multipotent stem cells. Whether IH stem cells are responsive to propranolol and are selectively targeted is unknown, and this is the focus of this study.
  
  
  METHODS
  IH stem cells were exposed to propranolol and were assayed for cellular and molecular alterations. We used endothelial cells (ECs) as controls and bone marrow-derived mesenchymal progenitor cells (bm-MPCs) as normal stem/progenitor counterparts to determine selectivity.
  
  
  RESULTS
  Our results show that propranolol significantly reduced IH stem cell growth but failed to induce caspase-3 activation. Normal bm-MPCs and mature ECs showed maintained or increased caspase-3 activation and significantly reduced cyclin-D1 levels. We further show that IH stem cells may escape apoptosis by inducing antiapoptotic pathways.
  
  
  CONCLUSIONS
  This study reveals that propranolol does not induce apoptosis in IH stem cells, which is in contrast with the result for ECs. Escape from apoptosis in IH stem cells may involve induction of antiapoptotic pathways.
authors.affiliation: Department of Pathology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Jina J Y
authors.initials: JJ
authors.lastname: Kum
authors.affiliation: 1] Department of Pathology, University of Western Ontario, London, Ontario, Canada [2] Metabolism and Diabetes Research Program, Lawson Health Research Institute, London, Ontario, Canada.
authors.forename: Zia A
authors.initials: ZA
authors.lastname: Khan
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D006391:Hemangioma / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007223:Infant; D039902:Multipotent Stem Cells / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000319:Adrenergic beta-Antagonists; D019938:Cyclin D1; D011433:Propranolol; D053148:Caspase 3