alexa Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo | OMICS International
ISSN: 1948-5956

Journal of Cancer Science & Therapy
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Research Article

Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor- Induced Wasting in a Murine Model of Cancer Cachexia In vivo

Ashley Wysong1,2, Scott A. Asher3, Xiaoying Yin3,8, Mitchell R. Gore3, Lisa Weinstein5, Denis C. Guttridge6, Albert S. Baldwin7,8,9, Marion E. Couch3,8 and Monte S. Willis4,5*

1Duke University School of Medicine, Durham, North Carolina

2Howard Hughes Medical Institute Medical Research Training Fellow, The Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina.

3Department of Otolaryngology-Head and Neck Surgery, University of North Carolina School of Medicine, Chapel Hill, North Carolina

4McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

5Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina

6Division of Human Cancer Genetics, Department of Molecular Virology, Immunology and Medical Genetics, Integrated Biomedical Graduate Program, Department of Pathology, and The Arthur G. James Comprehensive Cancer Center The Ohio State University, Columbus, Ohio

7Curriculum in Genetics and Molecular Biology, Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC

8Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

9Theralogics, Inc. Chapel Hill, North Carolina

*Corresponding Author:
Dr. Monte S. Willis, MD, PhD
Assistant Professor
Department of Pathology & Laboratory Medicine
McAllister Heart Institute
University of North Carolina
Medical Biomolecular Research Building
Rm 2336, 103 Mason Farm Road
Chapel Hill, NC, USA
Tel: (919) 843-1938
Fax: (919) 843- 4585
E-mail: [email protected]

Received date: October 22, 2010; Accepted date: November 17, 2010; Published date: December 15, 2010

Citation: Wysong A, Asher SA, Yin X, Gore MR, Weinstein L, et al. (2011) Selective Inhibition of NF-kappa-B with NBD Peptide Reduces Tumor-Induced Wasting in a Murine Model of Cancer Cachexia In vivo. J Cancer Sci Ther 3: 022-029. doi:10.4172/1948-5956.1000052

Copyright: © 2011 Wysong A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.

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 TNF?, 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-?B is highlighted in studies demonstrating that genetic inhibition of NF-?B 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.

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