The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer

Alexa Montoya, Armando Varela-Ramirez, Erin Dickerson, Eddy Pasquier, Alireza Torabi, Renato Aguilera, Zeina Nahleh, Brad Bryan

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Background: Substantial evidence supports the use of inexpensive β-AR antagonists (beta blockers) against a variety of cancers, and the β-AR antagonist propranolol was recently approved by the European Medicines Agency for the treatment of soft tissue sarcomas. Prospective and retrospective data published by our group and others suggest that non-selective β-AR antagonists are effective at reducing proliferative rates in breast cancers, however the mechanism by which this occurs is largely unknown. Methods: In this study, we measured changes in tumor proliferation and apoptosis in a late stage breast cancer patient treated with neoadjuvant propranolol. We expounded upon these clinical findings by employing an in vitro breast cancer model, where we used cell-based assays to evaluate propranolol-mediated molecular alterations related to cell proliferation and apoptosis. Results: Neoadjuvant propranolol decreased expression of the pro-proliferative Ki-67 and pro-survival Bcl-2 markers, and increased pro-apoptotic p53 expression in a patient with stage III breast cancer. Molecular analysis revealed that β-AR antagonism disrupted cell cycle progression and steady state levels of cyclins. Furthermore, propranolol treatment of breast cancer cells increased p53 levels, enhanced caspase cleavage, and induced apoptosis. Conclusion: Collectively, these data provide support for the incorporation of β-AR antagonists into the clinical management of breast cancer, and elucidate a partial molecular mechanism explaining the efficacy of β-AR antagonists against this disease.

Original languageEnglish (US)
Pages (from-to)155-165
Number of pages11
JournalBiomedical Journal
Volume42
Issue number3
DOIs
StatePublished - Jun 2019

Keywords

  • Apoptosis
  • Beta adrenergic receptor
  • Beta blockade
  • Breast cancer
  • Proliferation
  • Propranolol

PubMed: MeSH publication types

  • Journal Article

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