Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity

Busquets,Sílvia; Toledo,Míriam; Sirisi,Sònia; Orpí,Marcel; Serpe,Roberto; Coutinho,Joana; Martínez,Raquel; Argilés,Josep  Μ.; López-Soriano,Francisco  J.

doi:10.3892/etm.2011.260

Formoterol and cancer muscle wasting in rats: Effects on muscle force and total physical activity

Authors:
- Sílvia Busquets
- Míriam Toledo
- Sònia Sirisi
- Marcel Orpí
- Roberto Serpe
- Joana Coutinho
- Raquel Martínez
- Josep Μ. Argilés
- Francisco J. López-Soriano
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Affiliations: Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain, Department of Medical Oncology, University of Cagliari, 09124 Cagliari, Italy
Published online on: April 28, 2011 https://doi.org/10.3892/etm.2011.260
Pages: 731-735

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Abstract

Cancer cachexia occurs in the majority of cancer patients before death, and it is responsible for the death of 22% of cancer patients. One of the most relevant characteristics of cachexia is that of asthenia, which reflects significant muscle wasting noted in cachectic cancer patients The aim of the present study was to assess whether the β2-adrenergic agonist formoterol is associated with an improvement in physiological parameters such as grip force and total physical activity in cachetic rats. Administration of the β2-agonist formoterol (0.3 mg/kg for 7 days) in rats bearing Yoshida AH-130 ascites hepatoma tumors, a model which induces a strong loss of both body and muscle weight, resulted in a significant reversal of the muscle wasting process, as reflected by individual muscle weights. The anti-wasting effects of the drug were also observed in terms of total physical activity and grip force, thus resulting in an improvement in physical performance in cachectic tumor-bearing rats.

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1.	Warren S: The immediate causes of death in cancer. Am J Med Sci. 184:610–615. 1932. View Article : Google Scholar
2.	Argiles JM, Alvarez B and Lopez-Soriano FJ: The metabolic basis of cancer cachexia. Med Res Rev. 17:477–498. 1997. View Article : Google Scholar : PubMed/NCBI
3.	Argiles JM and Lopez-Soriano FJ: Why do cancer cells have such a high glycolytic rate? Med Hypotheses. 32:151–155. 1990. View Article : Google Scholar : PubMed/NCBI
4.	Harvey KB, Bothe A Jr and Blackburn GL: Nutritional assessment and patient outcome during oncological therapy. Cancer. 43:2065–2069. 1979. View Article : Google Scholar : PubMed/NCBI
5.	Nixon DW, Heymsfield SB, Cohen AE, et al: Protein-calorie undernutrition in hospitalized cancer patients. Am J Med. 68:683–690. 1980. View Article : Google Scholar : PubMed/NCBI
6.	DeWys W: Management of cancer cachexia. Semin Oncol. 12:452–460. 1985.
7.	Argiles JM, Garcia-Martinez C, Llovera M and Lopez-Soriano FJ: The role of cytokines in muscle wasting: its relation with cancer cachexia. Med Res Rev. 12:637–652. 1992. View Article : Google Scholar : PubMed/NCBI
8.	Van Royen M, Carbo N, Busquets S, et al: DNA fragmentation occurs in skeletal muscle during tumor growth: a link with cancer cachexia? Biochem Biophys Res Commun. 270:533–537. 2000.PubMed/NCBI
9.	Kim YS and Sainz RD: Beta-adrenergic agonists and hypertrophy of skeletal muscles. Life Sci. 50:397–407. 1992. View Article : Google Scholar : PubMed/NCBI
10.	Stock MJ and Rothwell NJ: Effects of beta-adrenergic agonists on metabolism and body composition. Control and Manipulation of Animal Growth. Buttery PJ, Hayes NB and Lindsay DB: Butterworths; London: pp. 249–257. 1985
11.	Agbenyega ET and Wareham AC: Effect of clenbuterol on skeletal muscle atrophy in mice induced by the glucocorticoid dexamethasone. Comp Biochem Physiol Comp Physiol. 102:141–145. 1992. View Article : Google Scholar : PubMed/NCBI
12.	Rajab P, Fox J, Riaz S, Tomlinson D, Ball D and Greenhaff PL: Skeletal muscle myosin heavy chain isoforms and energy metabolism after clenbuterol treatment in the rat. Am J Physiol Regul Integr Comp Physiol. 279:R1076–R1081. 2000.PubMed/NCBI
13.	Hinkle RT, Hodge KM, Cody DB, Sheldon RJ, Kobilka BK and Isfort RJ: Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor. Muscle Nerve. 25:729–734. 2002. View Article : Google Scholar : PubMed/NCBI
14.	Wineski LE, von Deutsch DA, Abukhalaf IK, Pitts SA, Potter DE and Paulsen DF: Muscle-specific effects of hindlimb suspension and clenbuterol in mature male rats. Cells Tissues Organs. 171:188–198. 2002. View Article : Google Scholar : PubMed/NCBI
15.	Yang YT and McElligott MA: Multiple actions of beta-adrenergic agonists on skeletal muscle and adipose tissue. Biochem J. 261:1–10. 1989.PubMed/NCBI
16.	Mersmann HJ: Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci. 76:160–172. 1998.PubMed/NCBI
17.	Anderson GP: Pharmacology of formoterol: an innovative bronchodilator. Agents Actions Suppl. 34:97–115. 1991.PubMed/NCBI
18.	Mahler DA: The effect of inhaled beta2-agonists on clinical outcomes in chronic obstructive pulmonary disease. J Allergy Clin Immunol. 110:S298–S303. 2002. View Article : Google Scholar : PubMed/NCBI
19.	Busquets S, Figueras MT, Fuster G, et al: Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting. Cancer Res. 64:6725–6731. 2004. View Article : Google Scholar : PubMed/NCBI
20.	Tessitore L, Costelli P, Bonetti G and Baccino FM: Cancer cachexia, malnutrition, and tissue protein turnover in experimental animals. Arch Biochem Biophys. 306:52–58. 1993. View Article : Google Scholar : PubMed/NCBI
21.	Sinis N, Guntinas-Lichius O, Irintchev A, et al: Manual stimulation of forearm muscles does not improve recovery of motor function after injury to a mixed peripheral nerve. Exp Brain Res. 185:469–483. 2008. View Article : Google Scholar : PubMed/NCBI
22.	Zangarelli A, Chanseaume E, Morio B, et al: Synergistic effects of caloric restriction with maintained protein intake on skeletal muscle performance in 21-month-old rats: a mitochondria-mediated pathway. FASEB J. 20:2439–2450. 2006. View Article : Google Scholar
23.	Fuster G, Busquets S, Ametller E, et al: Are peroxisome proliferator-activated receptors involved in skeletal muscle wasting during experimental cancer cachexia? Role of beta2-adrenergic agonists. Cancer Res. 67:6512–6519. 2007. View Article : Google Scholar
24.	Costelli P, Garcia-Martinez C, Llovera M, et al: Muscle protein waste in tumor-bearing rats is effectively antagonized by a beta 2-adrenergic agonist (clenbuterol). Role of the ATP-ubiquitin-dependent proteolytic pathway. J Clin Invest. 95:2367–2372. 1995. View Article : Google Scholar
25.	Ametller E, Busquets S, Fuster G, et al: Formoterol may activate rat muscle regeneration during cancer cachexia. Insciences J. 1:1–17. 2011. View Article : Google Scholar
26.	Lanigan C, Howes TQ, Borzone G, Vianna LG and Moxham J: The effects of beta 2-agonists and caffeine on respiratory and limb muscle performance. Eur Respir J. 6:1192–1196. 1993.PubMed/NCBI
27.	Signorile JF, Banovac K, Gomez M, Flipse D, Caruso JF and Lowensteyn I: Increased muscle strength in paralyzed patients after spinal cord injury: effect of beta-2 adrenergic agonist. Arch Phys Med Rehabil. 76:55–58. 1995. View Article : Google Scholar : PubMed/NCBI
28.	Marzabal M, Garcia-Martinez C, Comas J, Lopez-Soriano FJ and Argiles JM: A flow cytometric study of the rat Yoshida AH-130 ascites hepatoma. Cancer Lett. 72:169–173. 1993. View Article : Google Scholar : PubMed/NCBI
29.	Toledo M, Busquets S, Sirisi S, et al: Cancer cachexia: physical activity and muscle force in tumour-bearing rats. Oncol Rep. 25:189–193. 2011.PubMed/NCBI
30.	Argiles JM, Busquets S, Toledo M and Lopez-Soriano FJ: The role of cytokines in cancer cachexia. Curr Opin Support Palliat Care. 3:263–268. 2009. View Article : Google Scholar
31.	Llovera M, Garcia-Martinez C, Lopez-Soriano J, et al: Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol. 142:183–189. 1998. View Article : Google Scholar : PubMed/NCBI
32.	Argiles JM, Busquets S and Lopez-Soriano FJ: Cytokines as mediators and targets for cancer cachexia. Cancer Treat Res. 130:199–217. 2006. View Article : Google Scholar : PubMed/NCBI