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

Journal of Experimental & Clinical Cancer Research

Dayan B Goodenowe²  Hong Ma²  Pearson Ahiahonu²  Gerald F Davies¹  Dushmanthi Jayasinghe²  Shawn A Ritchie² 

[1] University of Saskatchewan, Saskatoon, Saskatchewan, Canada;Phenomenome Discoveries, Inc. Saskatoon, Saskatchewan, Canada

关键词: NFκB;    inflammation;    screening;    aging;    colorectal cancer;    Long-chain fatty acid;   

Others  :  827495
DOI  :  10.1186/1756-9966-30-59

 received in 2011-03-30, accepted in 2011-05-17,  发布年份 2011

【 摘 要 】

Background

Circulating 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.

Methods

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2011 Ritchie et al; licensee BioMed Central Ltd.

【 图 表 】

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