title: Human serum-derived hydroxy long-chain fatty acids exhibit anti-inflammatory and anti-proliferative activity.
abstract: 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.
authors.affiliation: Phenomenome Discoveries, Inc, Saskatoon, Saskatchewan, Canada. s.ritchie@phenomenome.com
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Ritchie
authors.forename: Dushmanthi
authors.initials: D
authors.lastname: Jayasinghe
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Davies
authors.forename: Pearson
authors.initials: P
authors.lastname: Ahiahonu
authors.forename: Hong
authors.initials: H
authors.lastname: Ma
authors.forename: Dayan B
authors.initials: DB
authors.lastname: Goodenowe
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005227:Fatty Acids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D051379:Mice; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D005227:Fatty Acids; D018836:Inflammation Mediators; D011065:Poly(ADP-ribose) Polymerases