Chemotherapy-induced muscle wasting: association with NF-κB Basic Applied Myology 18 (5): 139-148, 2008
Date
02/26/2008Abstract
A compounding feature of greater than 50% of all cancers is the high incidence of the
cachexia syndrome, a complex metabolic disorder characterized by extreme weight loss due
mainly to the gross depletion of skeletal muscle tissue. Although studies into the cause of
cancer cachexia has spanned over multiple decades, little is known about the effects of
various cancer treatments themselves on cachexia. For example, chemotherapy agents
induce side effects such as nausea and anorexia, but these symptoms do not fully account
for the changes seen with cancer cachexia. In this study we examine the effects of
chemotherapeutic compounds, specifically, cisplatin in the colon-26 adenocarcinoma model
of cancer cachexia. We find that although cisplatin is able to reduce tumor burden as
expected, muscle wasting in mice nevertheless persists. Strikingly, cisplatin alone was seen
to regulate muscle atrophy, which was independent of the commonly implicated ubiquitin
proteasome system. Finally, we show that cisplatin is able to induce NF-κB activity in both
mouse muscles and myotube cultures, suggesting that an additional side effect of cancer
treatment is the regulation of muscle wasting that may be mediated through activation of
the NF-κB signaling pathway.
Author List
Jeffrey S. Damrauer, Michael E. Stadler, Swarnali Acharyya, Albert S. Baldwin, Marion E. Couch, Denis C. GuttridgeAuthor
Michael Stadler MD Associate Dean, Chief Medical Officer, Associate P in the Medical College Physicians Administration department at Medical College of WisconsinView Online
