Benefits of β-blockers in cancer treatment

Arif, Mohamad; Hardianti, Mardiah Suci; Tyagita, Nurina; Safitri, Azizah Hikma

doi:10.5603/ocp.2022.0016

Cited by 5 publications

(3 citation statements)

References 99 publications

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“…There is now an abundance of additional data identifying specific tumorigenic roles of chronic stress-induced adrenergic pathways in promoting most of the well-established 'hallmarks' of cancer [16,17,19,37,40,48,49]. Although thorough reviews on the impacts of adrenergic signaling within various cancer types are available elsewhere [9,10,18,43,[50][51][52][53][54], a few foundational observations are worth highlighting. Several studies have appreciated that β2-AR knockout mice do not exhibit the enhanced tumor growth seen in chronically stressed control mice, suggesting the critical role of this specific receptor subtype in suppressing desirable anti-tumoral immune responses [16,46].…”

Section: Impact Of ß-Adrenergic Immune Modulation In Cancermentioning

confidence: 99%

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Switzer,

Puzanov,

Gandhi

et al. 2023

Melanoma Research

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The intricate pathways of the sympathetic nervous system hold an inherently protective role in the setting of acute stress. This is achieved through dynamic immunomodulatory and neurobiological networks. However, excessive and chronic exposure to these stress-induced stimuli appears to cause physiologic dysfunction through several mechanisms that may impair psychosocial, neurologic, and immunologic health. Numerous preclinical observations have identified the beta-2 adrenergic receptor (β2-AR) subtype to possess the strongest impact on immune dysfunction in the setting of chronic stressful stimuli. This prolonged expression of β2-ARs appears to suppress immune surveillance and promote tumorigenesis within multiple cancer types. This occurs through several pathways, including (1) decreasing the frequency and function of CD8 + T-cells infiltrating the tumor microenvironment (TME) via inhibition of metabolic reprogramming during T cell activation, and (2) establishing an immunosuppressive profile within the TME including promotion of an exhausted T cell phenotype while simultaneously enhancing local and paracrine metastatic potential. The use of nonselective β-AR antagonists appears to reverse many chronic stress-induced tumorigenic pathways and may also provide an additive therapeutic benefit for various immune checkpoint modulating agents including commonly utilized immune checkpoint inhibitors. Here we review the translational and clinical observations highlighting the foundational hypotheses that chronic stress-induced β-AR signaling promotes a pro-tumoral immunophenotype and that blockade of these pathways may augment the therapeutic response of immune checkpoint inhibition within the scope of melanoma.

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Section: Impact Of ß-Adrenergic Immune Modulation In Cancermentioning

confidence: 99%

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Switzer,

Puzanov,

Gandhi

et al. 2023

Melanoma Research

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“…44 Non-selective β-blockers such as propranolol and carvedilol are preferable than selective ones, such as atenolol, and nebivolol, since they inhibit all three types of β-adrenergic receptors. 45 Propranolol ([2-hydroxy-3-(naphthalen-1-yloxy)propyl](propan-2-yl) amine), the prototype of β-blockers, demonstrated invitro and in-vivo antiproliferative activity on human and murine melanoma cell lines, 46 as well as, it exhibited therapeutic efficacy in infantile hemangioma. 47 Propranolol treatment reduced the incidence of HCC in patients with alcoholic or HCV cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

“…β‐blockers were able to substantially obstruct stress‐triggered tumor growth and/or metastasis in preclinical studies 44 . Non‐selective β‐blockers such as propranolol and carvedilol are preferable than selective ones, such as atenolol, and nebivolol, since they inhibit all three types of β‐adrenergic receptors 45 . Propranolol ([2‐hydroxy‐3‐(naphthalen‐1‐yloxy)propyl](propan‐2‐yl)amine), the prototype of β‐blockers, demonstrated in‐vitro and in‐vivo antiproliferative activity on human and murine melanoma cell lines, 46 as well as, it exhibited therapeutic efficacy in infantile hemangioma 47 .…”

Section: Introductionmentioning

confidence: 99%

Anticancer effect of propranolol on diethylnitrosamine‐induced hepatocellular carcinoma rat model

Tamim,

Nagy,

Abdellah

et al. 2024

Fundamemntal Clinical Pharma

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BackgroundHepatocellular carcinoma (HCC) is the most widespread type of primary liver cancer. Diethylnitrosamine (DEN), a hepatotoxic hepatocarcinogenic compound, is used to induce HCC in animal models. The non‐selective β‐blocker propranolol demonstrated antiproliferative activity in many cancer types.ObjectiveThis investigation aimed to evaluate the anticancer effect of propranolol against DEN‐induced HCC in rats.MethodsThirty adult male rats were divided into the following groups: Group I (C, control), Group II (HCC); received DEN, 70 mg/kg body weight (b.wt.) once a week for 10 weeks, to induce HCC, and Group III (HCC/Prop); received DEN for 10 weeks for HCC induction, then received 20 mg/kg b.wt. propranolol, intraperitoneally for four successive weeks.ResultsHCC was developed in rats' livers and confirmed via significant liver architecture changes, significantly elevated activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), α‐fetoprotein (AFP), total‐ and direct‐bilirubin (Bil), and a decline in albumin (ALB) level in serum. HCC group demonstrated elevated levels of malondialdehyde (MDA), nitric oxide (NO), HIF‐1α, IL‐8, NF‐κB, PGE2, TGF‐β1, VEGF, and CD8, but significant decline of GSH, and IL‐10 level, with suppression of the antioxidant enzymes' activities. In addition, the gene expression of the hepatic inducible nitric oxide synthase (iNOS), and LAG‐3 were up‐regulated. Moreover, the protein expression of p‐PKC was up‐regulated, while that of PD‐1 and PD‐L1 were down‐regulated in the liver tissues of the HCC group. However, propranolol ameliorated the investigated parameters in the HCC/Prop group.ConclusionPropranolol exhibited an anticancer effect and thus can be considered as a promising treatment for HCC. Blocking of PD‐1/PD‐L1 and LAG‐3 signals participated in the anti‐tumor effect of propranolol on HCC.

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Stress und Krebs

Heikenwälder

2023

Der Moderne Krebs - Lifestyle Und Umweltfaktoren Als Risiko

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Benefits of β-blockers in cancer treatment

Cited by 5 publications

References 99 publications

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Targeting beta-adrenergic receptor pathways in melanoma: how stress modulates oncogenic immunity

Anticancer effect of propranolol on diethylnitrosamine‐induced hepatocellular carcinoma rat model

Stress und Krebs

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