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.
Bibliographical noteFunding Information:
This project was supported by grants to ZN ( CPRIT RP120528 ), ZN and BAB (TTUHSC seed grant #533701 ), and RJA and AVR (NIMHD RCMI 5G12MD007592 ).
© 2019 Chang Gung University
- Beta adrenergic receptor
- Beta blockade
- Breast cancer