The composition of linoleic acid and conjugated linoleic acid has potent synergistic effects on the growth and death of RAW264.7 macrophages: The role in anti-inflammatory effects

[Display omitted] •Combined linoleic acid (LA) or conjugated linoleic acid (CLA) synergistically suppressed cell growth in macrophages.•Combined LA and CLA decreased Ras, PI3K, Akt, MAPK, and mTOR and increased p21, p53, and Rb associated with cell growth.•Combined LA and CLA synergistically stimulated cell death associated with increased caspase-3 and cleaved caspase-3.•Combined LA and CLA synergistically suppressed cytokine production, including TNF-α, IL-6, and PGE2 in macrophages.•The effects of combined LA and CLA on cytokine production were associated with decreased COX-1, COX-2, and NF-κB p65. Linoleic acid (LA) is an omega-6 polyunsaturated fatty acid. Conjugated linoleic acid (CLA) is a family of LA isomers that includes both a trans fatty acid and a cis fatty acid. Both fatty acids play a nutritional role in maintaining health. Inflammation is critical in the pathogenesis of many diseases, including cancer. This study found that the combination of LA and CLA (LA/CLA), each of which had no effect, had a strong anti-synergistic effect on inflammatory macrophage RAW264.7 cells in vitro. Cells were cultured in a DMEM containing fetal bovine serum with or without either LA, CLA, or a combination of LA/CLA. The composition of LA and CLA at a comparatively lower concentration synergistically suppressed cell growth, resulting in a reduction in cell number. The underlying mechanism of this effect was based on reduced levels of Ras, PI3K, Akt, MAPK, and mTOR and elevated levels of p21, p53, and Rb, which are associated with cell growth. In addition, the combination of LA and CLA at a lower concentration stimulated potential cell death associated with increased caspase-3 and cleaved caspase-3 levels. Notably, this composition synergistically suppressed the production of TNF-α, IL-6, and PGE2, which are a major mediator of inflammation, with lipopolysaccharide stimulation in RAW264.7 cells This effect was associated with decreased levels of COX-1, COX-2, and NF-κB p65. This study may provide a useful tool for treating inflammatory conditions with the composition of LA and CLA.