Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity

GTAs were extracted from commercially available bulk human serum and then chromatographically separated into enriched (GTA-positive) and depleted (GTA-negative) fractions. SW620, MCF7 and LPS stimulated RAW264.7 cells were treated with various concentrations of the GTA-positive and GTA-negative extracts, and the effects on cell growth and inflammation determined.Enriched fractions resulted in poly-ADP ribose polymerase (PARP) cleavage, suppression of NFκB, induction of IκBα, and reduction in NOS2 mRNA transcript levels. In RAW264.7 mouse macrophage cells, incubation with enriched fractions prior to treatment with LPS blocked the induction of several pro-inflammatory markers including nitric oxide, TNFα, IL-1β, NOS2 and COX2.Our results show that human serum extracts enriched with endogenous long-chain hydroxy fatty acids possess anti-inflammatory and anti-proliferative activity. These findings support a hypothesis that the reduction of these metabolites with age may result in a compromised ability to defend against uncontrolled cell growth and inflammation, and could therefore represent a significant risk for the development of CRC.Fatty acid metabolism is intricately linked to the regulation of inflammatory processes, which underlie numerous diseases including cancer. For example, arachidonic, decosahexanoic and eicosapentanoic acids (AA, DHA and EPA) can be metabolized into both pro-inflammatory prostaglandins and leukotrienes, as well as into inflammation-resolving lipoxins, protectins and resolvins [1-3]. The failure to resolve acute inflammation through a lack of conversion to these latter products can result in a chronic inflammatory state, which over time can drive the development of inflammation-associated conditions including cancer, neurodegeneration, and others [4-10]. Functionally, many of these lipids have been shown to mediate their inflammation-associated effects through pathways involving the transcription factor NFκB and subsequent downstream pro-in