Oral resveratrol therapy inhibits cancer-induced skeletal muscle and cardiac atrophy in vivo

Scott Shadfar, Marion E. Couch, Kibwei A. McKinney, Lisa J. Weinstein, Xiaoying Yin, Jessica E. Rodriguez, Denis C. Guttridge, Monte Willis

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

The mechanism by which cancer mediates muscle atrophy has been delineated in the past 3 decades and includes a prominent role of tumor-derived cytokines, such as IL-6, TNF, and IL-1. These cytokines interact with their cognate receptors on muscle to activate the downstream transcription factor NF-B and induce sarcomere proteolysis. Experimentally, inhibiting NF-B signaling largely prevents cancer-induced muscle wasting, indicating its prominent role in muscle atrophy. Resveratrol, a natural phytoalexin found in the skin of grapes, has recently been shown to inhibit NF-B in cancer cells, which led us to hypothesize that it might have a protective role in cancer cachexia. Therefore, we investigated whether daily oral resveratrol could protect against skeletal muscle loss and cardiac atrophy in an established mouse model. We demonstrate resveratrol inhibits skeletal muscle and cardiac atrophy induced by C26 adenocarcinoma tumors through its inhibition of NF-B (p65) activity in skeletal muscle and heart. These studies demonstrate for the first time the utility of oral resveratrol therapy to provide clinical benefit in cancer-induced atrophy through the inhibition of NF-B in muscle. These findings may have application in the treatment of diseases with parallel pathophysiologies such as muscular dystrophy and heart failure.

Original languageEnglish (US)
Pages (from-to)749-762
Number of pages14
JournalNutrition and Cancer
Volume63
Issue number5
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Oncology
  • Nutrition and Dietetics
  • Cancer Research

Cite this

Shadfar, S., Couch, M. E., McKinney, K. A., Weinstein, L. J., Yin, X., Rodriguez, J. E., Guttridge, D. C., & Willis, M. (2011). Oral resveratrol therapy inhibits cancer-induced skeletal muscle and cardiac atrophy in vivo. Nutrition and Cancer, 63(5), 749-762. https://doi.org/10.1080/01635581.2011.563032