Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation

Vincenzo Musolino, Sandra Palus, Anika Tschirner, Cathleen Drescher, Micaela Gliozzi, Cristina Carresi, Cristiana Vitale, Carolina Muscoli, Wolfram Doehner, Stephan von Haehling, Stefan D. Anker, Vincenzo Mollace, Jochen Springer

Research output: Contribution to journalArticle

Abstract

Background: Cachexia is a complex metabolic syndrome associated with cancer. One of the features of cachexia is the loss of muscle mass, characterized by an imbalance between protein synthesis and protein degradation. Muscle atrophy is caused by the hyperactivation of some of the main cellular catabolic pathways, including autophagy. Cachexia also affects the cardiac muscle. As a consequence of the atrophy of the heart, cardiac function is impaired and mortality is increased. Anti-cachectic therapy in patients with cancer cachexia is so far limited to nutritional support and anabolic steroids. The use of the appetite stimulant megestrol acetate (MA) has been discussed as a treatment for cachexia. Methods: In this study the effects of MA were tested in cachectic tumour-bearing rats (Yoshida AH-130 ascites hepatoma). Rats were treated daily with 100mg/kg of MA or placebo starting one day after tumour inoculation, and for a period of 16days. Body weight and body composition were assessed at baseline and at the end of the study. Cardiac function was analysed by echocardiography at baseline and at day 11. Locomotor activity and food intake were assessed before tumour inoculation and at day 11. Autophagic markers were assessed in gastrocnemius muscle and heart by western blot analysis. Results: Treatment with 100mg/kg/day MA significantly attenuated the loss of body weight (-9±12%, P

Original languageEnglish
JournalJournal of Cachexia, Sarcopenia and Muscle
DOIs
Publication statusAccepted/In press - 2016

Keywords

  • Autophagy
  • Body composition
  • Cancer cachexia
  • Cardiac wasting
  • Heart failure
  • Megestrol acetate

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physiology (medical)

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    Musolino, V., Palus, S., Tschirner, A., Drescher, C., Gliozzi, M., Carresi, C., Vitale, C., Muscoli, C., Doehner, W., von Haehling, S., Anker, S. D., Mollace, V., & Springer, J. (Accepted/In press). Megestrol acetate improves cardiac function in a model of cancer cachexia-induced cardiomyopathy by autophagic modulation. Journal of Cachexia, Sarcopenia and Muscle. https://doi.org/10.1002/jcsm.12116