The beta adrenergic receptor antagonist propranolol alters mitogenic and apoptotic signaling in late stage breast cancer.
Apoptosis
Beta adrenergic receptor
Beta blockade
Breast cancer
Proliferation
Propranolol
Journal
Biomedical journal
ISSN: 2320-2890
Titre abrégé: Biomed J
Pays: United States
ID NLM: 101599820
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
28
02
2018
revised:
21
12
2018
accepted:
19
02
2019
entrez:
31
8
2019
pubmed:
31
8
2019
medline:
19
2
2020
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 31466709
pii: S2319-4170(18)30088-X
doi: 10.1016/j.bj.2019.02.003
pmc: PMC6717753
pii:
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Propranolol
9Y8NXQ24VQ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
155-165Informations de copyright
Copyright © 2019 Chang Gung University. Published by Elsevier B.V. All rights reserved.
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