Propranolol exhibits activity against hemangiomas independent of beta blockade
Autor: | Paula E. North, Shengnan Wu, Shikha Rao, Hartej Singh, Justin Elsey, Brian Pollack, Yoon Hee Jung, Jeffrey A. Bubley, Ming-Hui Zou, Jack L. Arbiser, Jayanth Kumar, Maiko Sasaki |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class Propranolol Pharmacology lcsh:RC254-282 Article Hemangioma Paediatric cancer 03 medical and health sciences 0302 clinical medicine In vivo 030225 pediatrics medicine cardiovascular diseases Receptor Beta (finance) Beta blocker business.industry medicine.disease lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens eye diseases 3. Good health Blockade 030104 developmental biology Oncology sense organs Stem cell business Tumour angiogenesis medicine.drug |
Zdroj: | npj Precision Oncology, Vol 3, Iss 1, Pp 1-9 (2019) NPJ Precision Oncology |
Popis: | Propranolol is a widely used beta blocker that consists of a racemic mixture of R and S stereoisomers. Only the S stereoisomer has significant activity against the beta-adrenergic receptor. A fortuitous clinical observation was made in an infant who received propranolol for cardiac disease, and regression of a hemangioma of infancy was noted. This has led to the widespread use of propranolol for the treatment of large and life-threatening hemangiomas of infancy. Infants receiving propranolol require monitoring to ensure that they do not suffer from side effects related to beta blockade. The exact mechanism of activity of propranolol in hemangioma of infancy is unknown. In this study, we treated hemangioma stem cells with both beta blockade active S- and inactive R-propranolol and looked for genes that were coordinately regulated by this treatment. Among the genes commonly downregulated, Angiopoietin-like 4 (ANGPTL4) was among the most regulated. We confirmed that propranolol isomers downregulated ANGPTL4 in endothelial cells, with greater downregulation of ANGPTL4 using the beta blockade inactive R-propranolol. ANGPTL4 is present in human hemangiomas of infancy. Finally, R-propranolol inhibited the growth of bEnd.3 hemangioma cells in vivo. The implication of this is that hemangioma growth can be blocked without the side effects of beta blockade. Given that humans have been exposed to racemic propranolol for decades and thus to R-propranolol, clinical development of R-propranolol for hemangiomas of infancy and other angiogenic diseases is warranted. |
Databáze: | OpenAIRE |
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