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Published on: May 3, 2021
The adrenergic receptor antagonists propranolol and carvedilol decrease bone sarcoma cell viability and sustained
Megan M Duckett1, Shee Kwan Phung1, Linh Nguyen1
1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul, Minnesota.
Abstract:
Adrenergic receptor (AR) expression has been demonstrated at several sites of primary and metastatic tumour growth and may influence proliferation, survival, metastasis and angiogenesis. AR antagonists like propranolol and carvedilol inhibit proliferation, induce apoptosis and synergize with chemotherapy agents in some cancers. Radiation resistance is mediated in many cells by upregulation of pro-survival pathways, which may be influenced by ARs. Studies evaluating AR antagonists combined with radiation are limited. The purpose of this study was to determine the effect of propranolol and carvedilol on viability and radiosensitivity in sarcoma cell lines. The hypothesis was that propranolol and carvedilol would increase radiosensitivity in four primary bone sarcoma cell lines. Single agent propranolol or carvedilol inhibited cell viability in all cell lines in a concentration-dependent manner. The mean inhibitory concentrations (IC50 ) for carvedilol were approximately 4-fold lower than propranolol and may be clinically relevant in vivo. Immunoblot analysis confirmed AR expression in both human and canine sarcoma cell lines; however, there was no correlation between baseline AR protein expression and radiosensitivity. Short duration treatment with carvedilol and propranolol did not significantly affect clonogenic survival. Prolonged exposure to propranolol and carvedilol significantly decreased the surviving fraction of canine osteosarcoma cells after 3Gy radiation. Based on our results and possible in vivo activity in dogs, further studies investigating the effects of carvedilol on sarcoma are warranted.
Insights
Adrenergic receptor antagonists, propranolol and carvedilol, reduced sarcoma cell viability. Prolonged exposure to these agents enhanced radiosensitivity in canine osteosarcoma cells, suggesting potential therapeutic applications.
Area of Science:
- Oncology
- Pharmacology
Background:
- Adrenergic receptors (ARs) are expressed in tumors and influence cancer progression.
- AR antagonists like propranolol and carvedilol show anti-cancer effects and may impact radiation resistance.
Purpose of the Study:
- To investigate the effects of propranolol and carvedilol on sarcoma cell viability and radiosensitivity.
- To determine if AR antagonists can enhance the efficacy of radiation therapy in sarcoma.
Main Methods:
- Cell viability assays were performed on four primary bone sarcoma cell lines treated with propranolol or carvedilol.
- Immunoblot analysis confirmed AR expression.
- Clonogenic survival assays assessed radiosensitivity after radiation exposure.
Main Results:
- Both propranolol and carvedilol inhibited cell viability in a dose-dependent manner, with carvedilol being more potent.
- AR expression was confirmed, but baseline levels did not correlate with radiosensitivity.
- Prolonged exposure to propranolol and carvedilol significantly increased radiosensitivity in canine osteosarcoma cells post-radiation.
Conclusions:
- Propranolol and carvedilol demonstrate anti-proliferative effects on sarcoma cells.
- Prolonged treatment with these AR antagonists can enhance radiosensitivity, particularly in canine osteosarcoma.
- Further research into carvedilol for sarcoma treatment is warranted, especially considering potential in vivo activity.
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