Megestrol acetate: its impact on muscle protein metabolism supports its use in cancer cachexia.
OBJECTIVE
Cachexia is a multiorganic syndrome associated with cancer, characterized by body weight loss, muscle and adipose tissue wasting and inflammation, being often associated with anorexia. The aim of the present investigation was to examine the effect of megestrol acetate (MA) in cachectic tumour-bearing animals analyzing changes in muscle proteolysis and in parameters related with quality of life.


METHODS
The effects of MA (100mg/kg) were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma).


RESULTS
Administration of MA to tumour-bearing rats resulted in an important reversal of the muscle wasting process, as reflected by individual muscle weights. MA also decreased the rate of protein degradation in incubated isolated skeletal muscles. Real-time PCR analysis revealed that MA treatment resulted in a decrease in ubiquitin, E2 and atrogin-1 mRNA content in muscles, therefore suggesting that the main anti-proteolytic action of the drug may be based on an inhibition of the ATP-ubiquitin-dependent proteolytic system. The drug also improves appetite, weight loss, total physical activity and grip force.


CONCLUSIONS
The results indicate that treatment with megestrol acetate increases appetite, weight loss, physical performance and muscle force in tumour-bearing rats suggesting that MA is a good candidate for muscle wasting treatment.
Busquets
Sílvia
S
Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Diagonal 645, 08028 Barcelona, Spain.
Serpe
Roberto
R
Sirisi
Sónia
S
Toledo
Míriam
M
Coutinho
Joana
J
Martínez
Raquel
R
Orpí
Marcel
M
López-Soriano
Francisco J
FJ
Argilés
Josep M
JM
D000818:Animals; D000855:Anorexia / Q000150:complications; D001066:Appetite / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000150:complications / Q000188:drug therapy*; D010450:Endopeptidases / Q000378:metabolism; D007249:Inflammation / Q000150:complications; D008297:Male; D019290:Megestrol Acetate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009124:Muscle Proteins / Q000187:drug effects / Q000378:metabolism*; D009133:Muscular Atrophy / Q000150:complications; D009369:Neoplasms / Q000150:complications*; D051381:Rats; D017208:Rats, Wistar
D009124:Muscle Proteins; C080306:ATP-ubiquitin-dependent proteinase; D010450:Endopeptidases; D019290:Megestrol Acetate