Effects of conjugated linoleic acid on myogenic and inflammatory responses in a human primary muscle and tumor coculture model

Nutr Cancer. 2009;61(5):687-95. doi: 10.1080/01635580902898750.

Abstract

The antiproliferative and anti-inflammatory properties of conjugated linoleic acid (CLA) make it a potentially novel treatment in chronic inflammatory muscle wasting disease, particularly cancer cachexia. Human primary muscle cells were grown in coculture with MIA PaCa-2 pancreatic tumor cells and exposed to varying concentrations of c9,t11 and t10,c12 CLA. Expression of myogenic (Myf5, MyoD, myogenin, and myostatin) and inflammatory genes (CCL-2, COX-2, IL-8, and TNF-alpha) were measured by real-time PCR. The t10,c12 CLA isomer, but not the c9,t11 isomer, significantly decreased MIA PaCa-2 proliferation by between 15% and 19%. There was a marked decrease in muscle MyoD and myogenin expression (78% and 62%, respectively), but no change in either Myf5 or myostatin, in myotubes grown in coculture with MIA PaCa-2 cells. CLA had limited influence on these responses. A similar pattern of myogenic gene expression changes was observed in myotubes treated with TNF-alpha alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF-alpha expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF-alpha in myotubes and could ameliorate its tumor-induced rise. The study provides insight into the anti-inflammatory and antiproliferative actions of CLA and its application as a therapeutic agent in inflammatory disease states.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Coculture Techniques
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation
  • Humans
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Isomerism
  • Linoleic Acids, Conjugated / pharmacology*
  • Male
  • Mice
  • Muscle Cells
  • Muscle Development / drug effects*
  • Muscle Development / genetics
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • RNA, Messenger / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Cytokines
  • Linoleic Acids, Conjugated
  • Muscle Proteins
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2