title: CLA reduces inflammatory mediators from A427 human lung cancer cells and A427 conditioned medium promotes differentiation of C2C12 murine muscle cells.
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.
authors.affiliation: Dipartimento di Medicina ed Oncologia Sperimentale, Università di Torino, Turin, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Oraldi
authors.forename: Marina
authors.initials: M
authors.lastname: Maggiora
authors.forename: Elena
authors.initials: E
authors.lastname: Paiuzzi
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Canuto
authors.forename: Giuliana
authors.initials: G
authors.lastname: Muzio
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015232:Dinoprostone / Q000276:immunology; D006736:Horses; D007211:Indoles / Q000494:pharmacology; D018836:Inflammation Mediators / Q000276:immunology*; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000276:immunology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D051379:Mice; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects*; D047492:Peroxisome Proliferator-Activated Receptors / Q000276:immunology; D002722:Chlorobenzenes
chemical_list: D016588:Anticarcinogenic Agents; D017077:Culture Media, Conditioned; D015232:Dinoprostone; D007211:Indoles; D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D044243:Linoleic Acids, Conjugated; D047492:Peroxisome Proliferator-Activated Receptors; C496197:trans-10,cis-12-conjugated linoleic acid; C060893:MK-886; D002722:Chlorobenzenes; C046938:9,11-linoleic acid