期刊
BIOMEDICAL JOURNAL
卷 42, 期 3, 页码 155-165出版社
ELSEVIER
DOI: 10.1016/j.bj.2019.02.003
关键词
Breast cancer; Propranolol; Beta blockade; Beta adrenergic receptor; Proliferation; Apoptosis
资金
- CPRIT [RP120528]
- TTUHSC [533701]
- NIMHD RCMI [5G12MD007592]
Background: Substantial evidence supports the use of inexpensive beta-AR antagonists (beta blockers) against a variety of cancers, and the beta-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 beta-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 beta-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 beta-AR antagonists into the clinical management of breast cancer, and elucidate a partial molecular mechanism explaining the efficacy of beta-AR antagonists against this disease.
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