Selective inhibition of NF-kappa-B with NBD peptide reduces tumor- induced wasting in a murine model of cancer cachexia in vivo

Ashley Wysong, Scott A. Asher, Xiaoying Yin, Mitchell R. Gore, Lisa Weinstein, Denis C. Guttridge, Albert S. Baldwin, Marion E. Couch, Monte Willis

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Cancer cachexia is a severe wasting syndrome characterized by the progressive loss of lean body mass and systemic inflammation, which is seen in as many as 80% of patients with advanced malignancy. It accounts for an estimated 20-30% of all cancer-related deaths. The mechanism by which cancer induces skeletal muscle atrophy in cachexia involves tumor-derived cytokines, including TNFα, IL-1, and IL-6. Upon interaction with their unique receptors on skeletal muscle, these cytokines activate NF-kappaB, a transcription factor crucial for atrophy related sarcomere proteolysis to occur. The significance of NF-κB is highlighted in studies demonstrating that genetic inhibition of NF-κB ameliorates cancer-induced muscle loss in vivo. In the present study, we evaluate a selective NF-kappaB inhibitor (NBD peptide) which targets the IkappaB complex to prevent cancer-induced skeletal muscle atrophy in an established mouse model (C26 adenocarcinoma). We identified for the first time that NBD peptide can directly inhibit tumor-induced NFkappaB activation in skeletal muscle, resulting in a decrease loss of lean muscle. We also identified that NBD peptide reduces the expression of the tumor induced ubiquitin ligases MuRF-1 and MAFbx/Atrogin-1 necessary for atrophy. These findings highlight that NBD peptide may be a potential selective therapeutic agent for the treatment of cancer cachexia.

Original languageEnglish (US)
Pages (from-to)22-29
Number of pages8
JournalJournal of Cancer Science and Therapy
Volume3
Issue number2
DOIs
StatePublished - Feb 11 2011
Externally publishedYes

Fingerprint

Cachexia
NF-kappa B
Peptides
Neoplasms
Skeletal Muscle
Muscular Atrophy
Atrophy
Muscle Neoplasms
Cytokines
Wasting Syndrome
Sarcomeres
Ligases
Ubiquitin
Interleukin-1
Proteolysis
Interleukin-6
Adenocarcinoma
Transcription Factors
Inflammation
Muscles

Keywords

  • Cachexia
  • Cancer
  • Muscle atrophy
  • NBD peptide
  • NF-kappa-B

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Selective inhibition of NF-kappa-B with NBD peptide reduces tumor- induced wasting in a murine model of cancer cachexia in vivo. / Wysong, Ashley; Asher, Scott A.; Yin, Xiaoying; Gore, Mitchell R.; Weinstein, Lisa; Guttridge, Denis C.; Baldwin, Albert S.; Couch, Marion E.; Willis, Monte.

In: Journal of Cancer Science and Therapy, Vol. 3, No. 2, 11.02.2011, p. 22-29.

Research output: Contribution to journalArticle

Wysong, Ashley ; Asher, Scott A. ; Yin, Xiaoying ; Gore, Mitchell R. ; Weinstein, Lisa ; Guttridge, Denis C. ; Baldwin, Albert S. ; Couch, Marion E. ; Willis, Monte. / Selective inhibition of NF-kappa-B with NBD peptide reduces tumor- induced wasting in a murine model of cancer cachexia in vivo. In: Journal of Cancer Science and Therapy. 2011 ; Vol. 3, No. 2. pp. 22-29.
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