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CLA Reduces Inflammatory Mediators from A427 Human Lung Cancer Cells and A427 Conditioned Medium Promotes Differentiation of C2C12 Murine Muscle Cells

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Lipids

Abstract

Conjugated linoleic acid (CLA) is thought to have anti-proliferative and anti-inflammatory properties, but its effect on cancer cachexia is unknown. Two effects were here investigated: that of CLA on inflammatory mediator production in human lung cancer cells, and that of reduced mediators on the myogenic differentiation of murine muscle C2C12 cells. The latter cells were grown in medium conditioned by human lung cancer A427 cells, with or without CLA, to mimic only the effect of molecules released from the tumor “in vivo”, excluding the effect of host-produced cachectic factors. The results obtained show that CLA was found to reduce the production of tumor necrosis factor-α, interleukin (IL)-1β and prostaglandin E2 (PGE2), but had no effect on IL-6 production. The mechanisms underlying the effect of CLA on cytokine or PGE2 release in A427 cells are probably mediated by activation of peroxisome proliferator-activated receptor (PPAR)α, which increased at 24 h CLA treatment. In turn, the reduced content of inflammatory mediators in medium conditioned by A427 cells, in the presence of CLA, allowed muscle cells to proliferate, again by inducing PPAR. The involvement of PPARα was demonstrated by treatment with the antagonist MK-886. The findings demonstrate the anti-inflammatory and myogenic action of CLA and point to its possible application as a novel dietary supplement and therapeutic agent in inflammatory disease states, such as cachexia.

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Abbreviations

CLA:

Conjugated linoleic acid

COX:

Cyclooxygenase

IL:

Interleukin

LDH:

Lactate dehydrogenase

PGE2:

Prostaglandin E2

PPAR:

Peroxisome proliferator-activated receptor

TNF:

Tumour necrosis factor

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Acknowledgments

This research was supported by grants from Compagnia di San Paolo, Italy, from Regione Piemonte, Italy and from the University of Turin, Italy. We thank Frances Cooper for revising the English and Prof. Sebastiano Colombatto for technical support.

Conflict of interest

All authors have read and agreed to the editorial policies, and declare that there are no financial or other conflicts of interest that might be construed to influence the results or interpretation of their manuscript.

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Authors and Affiliations

  1. Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Corso Raffello 30, 10125, Turin, Italy

    Manuela Oraldi, Marina Maggiora, Elena Paiuzzi, Rosa A. Canuto & Giuliana Muzio

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  1. Manuela Oraldi
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  2. Marina Maggiora
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  3. Elena Paiuzzi
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  4. Rosa A. Canuto
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  5. Giuliana Muzio
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Correspondence to Rosa A. Canuto.

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Oraldi, M., Maggiora, M., Paiuzzi, E. et al. CLA Reduces Inflammatory Mediators from A427 Human Lung Cancer Cells and A427 Conditioned Medium Promotes Differentiation of C2C12 Murine Muscle Cells. Lipids 48, 29–38 (2013). https://doi.org/10.1007/s11745-012-3734-6

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  • DOI: https://doi.org/10.1007/s11745-012-3734-6

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