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

Abstract

BackgroundCirculating levels of novel long-chain hydroxy fatty acids (called GTAs) were recently discovered in the serum of healthy subjects which were shown to be reduced in subjects with colorectal cancer (CRC), independent of tumor burden or disease stage. The levels of GTAs were subsequently observed to exhibit an inverse association with age in the general population. The current work investigates the biological activity of these fatty acids by evaluating the effects of enriched human serum extracts on cell growth and inflammation.MethodsGTAs 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.ResultsEnriched 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.ConclusionsOur 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.

Interaction of ω-3 polyunsaturated fatty acids with radiation therapy in two different colorectal cancer cell lines

“…29 u-3 PUFAs could inhibit CRC cell proliferation with a decrease in proinflammatory proteins, including iNOS and COX-2. 30 Furthermore, long-term intake of COX-2 inhibitor was effective in decreasing colorectal cancer risk. 31 These observations indicate that COX-2 does not only play an important role in promoting tumor cell growth but also is a potential target for anti-cancer treatment.…”

Metabolomic Profiling in Colorectal Cancer: Opportunities for Personalized Medicine

“…Several pioneers have provided some examples of translating metabolomic-based markers into clinical practice. After observing the decreased concentration of hydroxylated polyunsaturated ultra-long-chain fatty acids in the serum of CRC patients in metabolomic studies [23], Ritchie performed cell studies in order to investigate the biological relevance [85], exhibiting the anti-inflammatory and antiproliferative activity of these metabolites. The reduction of the metabolites represented a significant risk for the development of CRC.…”

Biomarkers intersect with the exposome

“…The final study highlights work by Ritchie and coworkers to discover biomarkers of colorectal cancer (CRC) (Ritchie et al 2010a,b; Ritchie et al 2011). Using untargeted measurements of several thousand small non-polar molecules in serum from three independent case-control studies, the investigators reported a set of 13 common features that were strongly associated with CRC.…”