Format

Send to

Choose Destination
J Cancer Res Clin Oncol. 2017 Feb;143(2):275-291. doi: 10.1007/s00432-016-2278-1. Epub 2016 Oct 5.

β-Adrenergic modulation of cancer cell proliferation: available evidence and clinical perspectives.

Author information

1
Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal.
2
I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
3
Center for Research in Medical Pharmacology, University of Insubria, Varese, Italy.
4
Department of Medical Education and Simulation, Faculty of Medicine, University of Porto, Porto, Portugal.
5
Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal. lribeiro@med.up.pt.
6
I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal. lribeiro@med.up.pt.
7
Department of Medical Education and Simulation, Faculty of Medicine, University of Porto, Porto, Portugal. lribeiro@med.up.pt.

Abstract

PURPOSE:

In this review, we aimed to present and discuss the available preclinical and epidemiological evidences regarding the modulation of cancer cell proliferation by β-adrenoceptors (β-AR), with a specific focus on the putative effects of β-blockers according to their pharmacological properties.

METHODS:

A comprehensive review of the published literature was conducted, and the evidences concerning the involvement of β-AR in cancer as well as the possible role of β-blockers were selected and discussed.

RESULTS:

The majority of reviewed studies show that: (1) All the cancer types express both β1- and β2-AR, with the exception of neuroblastoma only seeming to express β2-AR; (2) adrenergic agonists are able to increase proliferation of several types of cancers; (3) the proliferative effect seems to be mediated by both β1- and β2-AR; (4) binding to β-AR results in a cAMP transient flux which activates two major downstream effector systems: protein kinase A and EPAC and (5) β-blockers might be putative adjuvants for cancer treatment.

CONCLUSIONS:

Overall, the reviewed studies show strong evidences that β-AR activation, through several intracellular mechanisms, modulate tumor cell proliferation suggesting β-blockers can be a feasible therapeutic approach to antagonize β-adrenergic response or have a protective effect per se. This review highlight the need for intensifying the research not only on the molecular mechanisms underlying the β-adrenergic influence in cancer, but also on the implications of biased agonism of β-blockers as potential antitumor agents.

KEYWORDS:

Adrenergic system; Cancer; Catecholamines; Proliferation; β-Blockers

PMID:
27709364
DOI:
10.1007/s00432-016-2278-1
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center