Effects of Conjugated Linoleic Acid on Myogenic and Inflammatory Responses in a Human Primary Muscle and Tumor Coculture Model

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-α) 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-α alone. Several-fold significant increases in CCL-2, COX-2, IL-8, and TNF-α expression in myotubes were observed with MIA PaCa-2 coculture. The c9,t11 CLA isomer significantly decreased basal expression of TNF-α 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.

ACKNOWLEDGMENTS

The authors acknowledge the support by the Geoffrey Gardiner Dairy Foundation Ltd. (Grant Code GF4/018) for the funding of this project. The research was conducted in the School of Exercise and Nutrition Sciences, Deakin University, Burwood, Australia.

Notes

^a Abbreviations are as follows: CCL-2, chemokine (C-C motif) ligand 2; COX-2, cyclooxygenase-2; IL-8, interleukin-8; TNF-α, tumor necrosis factor-alpha.

^a Abbreviation is as follows: TNF-α, tumor necrosis factor-alpha.

^b Values are expressed as percentage change of 3 different human cell lines grown in triplicate relative to primary human muscle cells in the absence of TNF-α or MIA PaCa-2.