Induction of proteasome expression in skeletal muscle is attenuated by inhibitors of NF-κB activation


The potential for inhibitors of nuclear factor-κB (NF-κB) activation to act as inhibitors of muscle protein degradation in cancer cachexia has been evaluated both in vitro and in vivo. Activation of NF-κB is important in the induction of proteasome expression and protein degradation by the tumour factor, proteolysis-inducing factor (PIF), since the cell permeable NF-κB inhibitor SN50 (18 μM) attenuated the expression of 205 proteasome α-subunits, two subunits of the 195 regulator MSSI and p42, and the ubiquitin-conjugating enzyme, E214k, as well as the decrease in myosin expression in murine myotubes. To assess the potential therapeutic benefit of NF-κB inhibitors on muscle atrophy in cancer cachexia, two potential inhibitors were employed; curcumin (50 μM) and resveratrol (30 μM). Both agents completely attenuated total protein degradation in murine myotubes at all concentrations of PIF, and attenuated the PIF-induced increase in expression of the ubiquitin-proteasome proteolytic pathway, as determined by the 'chymotrypsin-like' enzyme activity, proteasome subunits and E2 14k. However, curcumin (150 and 300 mg kg-1) was ineffective in preventing weight loss and muscle protein degradation in mice bearing the MAC16 tumour, whereas resveratrol (1 mg kg-1) significantly attenuated weight loss and protein degradation in skeletal muscle, and produced a significant reduction in NF-κB DNA-binding activity. The inactivity of curcumin was probably due to a low bioavailability. These results suggest that agents which inhibit nuclear translocation of NF-κB may prove useful for the treatment of muscle wasting in cancer cachexia.

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Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences
Additional Information: © 2004 Cancer Research UK Creative Commons Attribution-NonCommercial-Share-Alike 3.0 licence, subject to the conditions listed at
Uncontrolled Keywords: cancer cachexia,muscle wasting,NF-κB,proteasome expression,Cancer Research,Oncology
Publication ISSN: 1532-1827
Last Modified: 20 Feb 2024 08:06
Date Deposited: 19 Aug 2019 08:50
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://www.natu ... l/6602165a.html (Publisher URL)
PURE Output Type: Article
Published Date: 2004-10-26
Authors: Wyke, S.M.
Russell, Steve T. (ORCID Profile 0000-0002-5491-900X)
Tisdale, Michael J.

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