Related Experiment Video
Updated: Aug 29, 2025
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Propranolol blocks osteosarcoma cell cycle progression, inhibits angiogenesis and slows xenograft growth in
Luisina M Solernó1,2, Natasha T Sobol1,2, María F Gottardo1,2
1Center for Molecular and Translational Oncology (COMTra), Science and Technology Department, National University of Quilmes, Buenos Aires, Argentina.
Abstract:
Osteosarcoma is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates, especially in low- and middle-income countries. Despite multiple efforts to repurpose β-blocker propranolol in oncology, its potential application in osteosarcoma management remains largely unexplored. Considering the unsatisfied clinical needs of this aggressive disease, we evaluated the antitumoral activity of propranolol using different in vitro and in vivo osteosarcoma preclinical models, alone or in addition to chemotherapy. Propranolol significantly impaired cellular growth in β2-adrenergic receptor-expressing MG-63 and U-2OS cells, and was capable of blocking growth-stimulating effects triggered by catecholamines. siRNA-mediated ADRB2 knockdown in MG-63 cells was associated with decreased cell survival and a significant attenuation of PPN anti-osteosarcoma activity. Direct cytostatic effects of propranolol were independent of apoptosis induction and were associated with reduced mitosis, G0/G1 cell cycle arrest and a significant down-regulation of cell cycle regulator Cyclin D1. Moreover, colony formation, 3D spheroid growth, cell chemotaxis and capillary-like tube formation were drastically impaired after propranolol treatment. Interestingly, anti-migratory activity of β-blocker was associated with altered actin cytoskeleton dynamics. In vivo, propranolol treatment (10 mg/kg/day i.p.) reduced the early angiogenic response triggered by MG-63 cells in nude mice. Synergistic effects were observed in vitro after combining propranolol with chemotherapeutic agent cisplatin. Sustained administration of propranolol (10 mg/kg/day i.p., five days a week), alone and especially in addition to low-dose metronomic cisplatin (2 mg/kg/day i.p., three times a week), markedly reduced xenograft progression. After histological analysis, propranolol and cisplatin combination resulted in low tumor mitotic index and increased tumor necrosis. β-blockade using propranolol seems to be an achievable and cost-effective therapeutic approach to modulate osteosarcoma aggressiveness. Further translational studies of propranolol repurposing in osteosarcoma are warranted.
Insights
The beta-blocker propranolol shows promise in treating osteosarcoma by inhibiting tumor cell growth and migration. Combining propranolol with chemotherapy may offer a cost-effective approach to reduce osteosarcoma progression.
Area of Science:
- Oncology
- Pharmacology
Background:
- Osteosarcoma presents a significant clinical challenge with limited treatment efficacy and high mortality, particularly in resource-limited settings.
- The therapeutic potential of beta-blocker propranolol in osteosarcoma remains largely uninvestigated despite its repurposing efforts in other cancers.
Purpose of the Study:
- To evaluate the antitumoral activity of propranolol in preclinical osteosarcoma models, both as a single agent and in combination with chemotherapy.
- To investigate the mechanisms underlying propranolol's effects on osteosarcoma cell behavior and tumor growth.
Main Methods:
- In vitro studies utilized osteosarcoma cell lines (MG-63, U-2OS) to assess propranolol's effects on cell growth, cell cycle, apoptosis, colony formation, and spheroid growth.
- In vivo studies involved nude mice xenograft models to evaluate propranolol's impact on tumor progression and angiogenesis, alone and combined with cisplatin.
- siRNA-mediated knockdown of the beta-2 adrenergic receptor (ADRB2) was employed to elucidate the role of this receptor in propranolol's activity.
Main Results:
- Propranolol demonstrated significant cytostatic effects, inhibiting cell proliferation and inducing G0/G1 cell cycle arrest, notably down-regulating Cyclin D1.
- The drug impaired key cancer hallmarks including colony formation, 3D spheroid growth, chemotaxis, and angiogenesis, with anti-migratory effects linked to actin cytoskeleton modulation.
- In vivo, propranolol reduced tumor growth and angiogenesis, with combination therapy (propranolol + metronomic cisplatin) showing synergistic effects, leading to reduced tumor progression, mitotic index, and increased necrosis.
Conclusions:
- Beta-blockade with propranolol is a potential therapeutic strategy to mitigate osteosarcoma aggressiveness by targeting cell proliferation, migration, and angiogenesis.
- Combination therapy of propranolol with chemotherapy, particularly low-dose metronomic cisplatin, presents a promising, cost-effective approach for osteosarcoma management.
- Further translational research is warranted to explore the repurposing of propranolol for osteosarcoma treatment.
Related Concept Videos
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
02:34Inhibition of Cdk Activity