Aerobic Exercise and Pharmacological Treatments Counteract Cachexia by Modulating Autophagy in Colon Cancer View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-07

AUTHORS

Eva Pigna, Emanuele Berardi, Paola Aulino, Emanuele Rizzuto, Sandra Zampieri, Ugo Carraro, Helmut Kern, Stefano Merigliano, Mario Gruppo, Mathias Mericskay, Zhenlin Li, Marco Rocchi, Rosario Barone, Filippo Macaluso, Valentina Di Felice, Sergio Adamo, Dario Coletti, Viviana Moresi

ABSTRACT

Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify the pathways involved in the physical activity-mediated rescue of skeletal muscle mass and function, we investigated the effects of voluntary exercise on cachexia in colon carcinoma (C26)-bearing mice. Voluntary exercise prevented loss of muscle mass and function, ultimately increasing survival of C26-bearing mice. We found that the autophagic flux is overloaded in skeletal muscle of both colon carcinoma murine models and patients, but not in running C26-bearing mice, thus suggesting that exercise may release the autophagic flux and ultimately rescue muscle homeostasis. Treatment of C26-bearing mice with either AICAR or rapamycin, two drugs that trigger the autophagic flux, also rescued muscle mass and prevented atrogene induction. Similar effects were reproduced on myotubes in vitro, which displayed atrophy following exposure to C26-conditioned medium, a phenomenon that was rescued by AICAR or rapamycin treatment and relies on autophagosome-lysosome fusion (inhibited by chloroquine). Since AICAR, rapamycin and exercise equally affect the autophagic system and counteract cachexia, we believe autophagy-triggering drugs may be exploited to treat cachexia in conditions in which exercise cannot be prescribed. More... »

PAGES

26991

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/srep26991

DOI

http://dx.doi.org/10.1038/srep26991

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023098210

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27244599


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463 https://www.grid.ac/institutes/grid.12711.34 schema:alternateName University of Urbino
464 schema:name Department of Biomolecular Sciences, Unit of Biostatistics, "Carlo Bo" University of Urbino, Italy.
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466 https://www.grid.ac/institutes/grid.417109.a schema:alternateName Wilhelminen Hospital
467 schema:name Department of Biomedical Sciences, University of Padua, Italy.
468 Ludwig Boltzmann Institute of Electrical Stimulation and Physical Rehabilitation, Department of Physical Medicine and Rehabilitation, Wilhelminenspital Wien, Austria.
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471 schema:name DAHFMO Unit of Histology and Medical Embryology, Interuniversity Institute of Myology, Sapienza University of Rome, Italy.
472 Department of Biological Adaptation and Ageing B2A (CNRS UMR 8256 - INSERM ERL U1164 - UPMC P6), Pierre et Marie Curie University, Paris 6, France.
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475 schema:name IRCCS Fondazione Ospedale San Camillo, Venezia, Italy.
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478 schema:name DAHFMO Unit of Histology and Medical Embryology, Interuniversity Institute of Myology, Sapienza University of Rome, Italy.
479 Department of Kinesiology, Research Group in Exercise Physiology, KU Leuven, Belgium.
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481 https://www.grid.ac/institutes/grid.5608.b schema:alternateName University of Padua
482 schema:name Department of Surgical and Gastroenterological Sciences, University of Padua, Italy.
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484 https://www.grid.ac/institutes/grid.7841.a schema:alternateName Sapienza University of Rome
485 schema:name DAHFMO Unit of Histology and Medical Embryology, Interuniversity Institute of Myology, Sapienza University of Rome, Italy.
486 Department of Mechanical &Aerospace Engineering, Sapienza University of Rome, Italy.
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