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REVIEW ARTICLE

Propranolol: Repurposing an old drug to modulate tumor growth, angiogenesis, and immunity in hepatocellular carcinoma

Iman Owliaee1 ,  Mehran Khaledian2 ,  Faezeh Ramezani3 ,  Ali Shojaeian4*
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1 Department of Medical Virology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
2 Department of Medical Entomology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
3 Division of Medical Biotechnology, Department of Medical Laboratory Sciences, School of Paramedical Sciences, Shiraz, Iran
4 Research Center for Molecular Medicine, Institute of Cancer, Avicenna Health Research Institute, Hamadan University of Medical Sciences, Hamadan, Iran
JCTR, 025080010 https://doi.org/10.36922/JCTR025080010
Received: 18 February 2025 | Revised: 29 April 2025 | Accepted: 28 May 2025 | Published online: 19 June 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the key risk determinants for hepatocellular carcinoma (HCC), which is a significant public health issue worldwide. Molecular mechanisms of HBV- and HCV-related hepatocarcinogenesis are reviewed here, together with the therapeutic potential of propranolol against HCC. HBV and HCV promote HCC development through chronic inflammation, oxidative stress, and dysregulation of signaling pathways involved in proliferation, apoptosis, and immunity. Propranolol demonstrates promise in inhibiting tumor growth, angiogenesis, and metastasis in HCC by modulating adrenergic receptors and the immune response. Evidence suggests propranolol reduces inflammatory cytokines, enhances natural killer cell activity, and decreases the expression of immune checkpoint proteins such as programmed cell death protein 1 and T cell immunoglobulin and mucin domain-containing protein-3 in HCC cells. Clinical studies indicate that propranolol may lower HCC incidence and improve survival in cirrhotic patients. However, optimal dosing, long-term safety, and efficacy require further research through large randomized controlled trials. Aim: This paper aims to review the potential of propranolol as an adjuvant therapy for HBV/HCV-induced HCC by examining its antitumor, anti-angiogenic, and immunomodulatory effects. Conclusion: Propranolol represents a prospective adjuvant therapy for HBV/HCV-induced HCC that warrants continued investigation to fully elucidate its therapeutic potential against this disease. Relevance for patients: Propranolol may improve outcomes in HBV/HCV-related HCC by reducing tumor growth, angiogenesis, and immune evasion, offering a potential adjunct therapy to enhance patient survival and prognosis.

Keywords
Hepatocellular carcinoma
Hepatitis B virus
Hepatitis C virus
Propranolol
Cirrhosis
Funding
None.
Conflict of interest
The authors declare that they have no conflicts of interest.
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