This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Busquets, S. Articles by López-Soriano, F. J. Search for Related Content PubMed PubMed Citation Articles by Busquets, S. Articles by López-Soriano, F. J.

Anticachectic Effects of Formoterol

A Drug for Potential Treatment of Muscle Wasting

Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain

In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the ß₂-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effects of the drug were based on both an activation of the rate of protein synthesis and an inhibition of the rate of muscle proteolysis. Northern blot analysis revealed that formoterol treatment resulted in a decrease in the mRNA content of ubiquitin and proteasome subunits in gastrocnemius muscles; this, together with the decreased proteasome activity observed, suggest that the main anti-proteolytic action of the drug may be based on an inhibition of the ATP-ubiquitin-dependent proteolytic system. Interestingly, the ß₂-agonist was also able to diminish the increased rate of muscle apoptosis (measured as DNA laddering as well as caspase-3 activity) present in tumor-bearing animals. The present results indicate that formoterol exerted a selective, powerful protective action on heart and skeletal muscle by antagonizing the enhanced protein degradation that characterizes cancer cachexia, and it could be revealed as a potential therapeutic tool in pathologic states wherein muscle protein hypercatabolism is a critical feature such as cancer cachexia or other wasting diseases.

This article has been cited by other articles:

				G. S. Lynch and J. G. Ryall Role of {beta}-Adrenoceptor Signaling in Skeletal Muscle: Implications for Muscle Wasting and Disease Physiol Rev, April 1, 2008; 88(2): 729 - 767. [Abstract] [Full Text] [PDF]

				L. Radbruch, F. Strasser, F. Elsner, J. F. Goncalves, J. Loge, S. Kaasa, F. Nauck, P. Stone, and the Research Steering Committee of the European As Fatigue in palliative care patients -- an EAPC approach Palliative Medicine, January 1, 2008; 22(1): 13 - 32. [Abstract] [PDF]

				G. Fuster, S. Busquets, E. Ametller, M. Olivan, V. Almendro, C. C. Fontes de Oliveira, M. Figueras, F. J. Lopez-Soriano, and J. M. Argiles Are Peroxisome Proliferator-Activated Receptors Involved in Skeletal Muscle Wasting during Experimental Cancer Cachexia? Role of {beta}2-Adrenergic Agonists Cancer Res., July 1, 2007; 67(13): 6512 - 6519. [Abstract] [Full Text] [PDF]

				D. J. Baker, D. Constantin-Teodosiu, S. W. Jones, J. A. Timmons, and P. L. Greenhaff Chronic Treatment with the beta2-Adrenoceptor Agonist Prodrug BRL-47672 Impairs Rat Skeletal Muscle Function by Inducing a Comprehensive Shift to a Faster Muscle Phenotype J. Pharmacol. Exp. Ther., October 1, 2006; 319(1): 439 - 446. [Abstract] [Full Text] [PDF]

				P. Costelli, M. Muscaritoli, M. Bossola, F. Penna, P. Reffo, A. Bonetto, S. Busquets, G. Bonelli, F. J. Lopez-Soriano, G. B. Doglietto, et al. IGF-1 is downregulated in experimental cancer cachexia Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2006; 291(3): R674 - R683. [Abstract] [Full Text] [PDF]