Document Detail


Involvement of α2- and β2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation.
MedLine Citation:
PMID:  22122228     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: β-Adrenoceptors are expressed in human and experimental animal breast cancer cells. However, the effect of the agonists and antagonists reported on cell proliferation and tumour growth was paradoxical, precluding their utilization as possible adjuvant therapy, mainly in the cases of refractory tumours.
EXPERIMENTAL APPROACH: β-Adrenoceptor expression was analysed by immunofluorescence and RT-PCR. Cell proliferation was assessed by [(3) H]-thymidine incorporation, tumour growth by measuring with a calliper and ERK 1/2 phosphorylation by Western blotting.
KEY RESULTS: β(2) -Adrenoceptor expression was confirmed in the mouse and human cells tested. Cell proliferation was increased by adrenaline (by α(2) -adrenoceptor action) and decreased in every tested cell line by the β-adrenoceptor agonist isoprenaline and the β(2) -adrenoceptor agonist salbutamol. Isoprenaline and salbutamol reduced tumour growth in every tumour tested (mouse C4-HD and CC4-3-HI and human IBH-4, IBH-6 and MDA-MB-231 cell lines growing as xenografts in nude mice). These effects were reversed by the β-adrenoceptor antagonist propranolol. The α(2) -adrenoceptor antagonist rauwolscine and the β(2) -adrenoceptor agonist salbutamol were equally effective in diminishing tumour growth. ERK 1/2 activation analysed in IBH-4 tumours correlated with tumour growth, with the β-adrenoceptor agonists decreasing its activation. Inhibition of ERK 1/2 phosphorylation in vitro was mainly mediated by the PKA pathway.
CONCLUSIONS AND IMPLICATIONS: In our experimental models, the β-adrenoceptor agonists inhibited breast cancer cell proliferation and tumour growth, probably mediated by inhibition of ERK 1/2 phosphorylation. The β-adrenoceptor agonists were as effective as the α(2) -adrenoceptor antagonist rauwolscine, providing possible novel adjuvant treatments for breast cancer.
Authors:
C Pérez Piñero; A Bruzzone; M G Sarappa; L F Castillo; I A Lüthy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  166     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-16     Completed Date:  2012-09-07     Revised Date:  2013-05-02    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  721-36     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Instituto de Biología y Medicina Experimental - CONICET, Vuelta de Obligado 2490, C1428ADN Ciudad Autónoma de Buenos Aires, Argentina.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic Agonists / pharmacology,  therapeutic use*
Adrenergic Antagonists / pharmacology,  therapeutic use
Albuterol / pharmacology
Animals
Antineoplastic Agents / pharmacology,  therapeutic use*
Breast Neoplasms / drug therapy*,  metabolism,  pathology
Cell Line, Tumor
Cell Proliferation / drug effects
Female
Humans
Isoproterenol / pharmacology
Mice
Mice, Inbred BALB C
Mice, Nude
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Propranolol / pharmacology
Receptors, Adrenergic, alpha-2 / metabolism*
Receptors, Adrenergic, beta-2 / metabolism*
Xenograft Model Antitumor Assays
Yohimbine / pharmacology
Chemical
Reg. No./Substance:
0/Adrenergic Agonists; 0/Adrenergic Antagonists; 0/Antineoplastic Agents; 0/Receptors, Adrenergic, alpha-2; 0/Receptors, Adrenergic, beta-2; 146-48-5/Yohimbine; 18559-94-9/Albuterol; 525-66-6/Propranolol; 7683-59-2/Isoproterenol; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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