title: Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens.
abstract: BACKGROUND
  To develop effective strategies in cancer chemoprevention, an increased understanding of endogenous biochemical mediators that block metastatic processes is critically needed. Dietary lipids and non-steroidal anti-inflammatory drugs (NSAIDs) have a published track record of providing protection against gastrointestinal malignancies. In this regard, we examined the effects of membrane plasmalogens and ibuprofen on regulation of cellular levels of diamines, polyamine mediators that are augmented in cancer cells. For these studies we utilized Chinese hamster ovary (CHO) cells and NRel-4 cells, a CHO cell line with defective plasmalogen synthesis.
  
  
  RESULTS
  NRel-4 cells, which possess cellular plasmalogen levels that are 10% of control CHO cells, demonstrated 2- to 3-fold increases in cellular diamine levels. These diamine levels were normalized by plasmalogen replacement and significantly reduced by ibuprofen. In both cases the mechanism of action appears to mainly involve increased diamine efflux via the diamine exporter. The actions of ibuprofen were not stereospecific, supporting previous studies that cyclooxygenase (COX) inhibition is unlikely to be involved in the ability of NSAIDs to reduce intracellular diamine levels.
  
  
  CONCLUSIONS
  Our data demonstrate that ibuprofen, a drug known to reduce the risk of colorectal cancer, reduces cellular diamine levels via augmentation of diamine efflux. Similarly, augmentation of membrane plasmalogens can increase diamine export from control and plasmalogen-deficient cells. These data support the concept that membrane transporter function may be a therapeutic point of intervention for dietary and pharmacological approaches to cancer chemoprevention.
authors.affiliation: Dept of Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy, Harrogate, TN 37752, USA. paul.wood@lmunet.edu
authors.forename: Paul L
authors.initials: PL
authors.lastname: Wood
authors.forename: M Amin
authors.initials: MA
authors.lastname: Khan
authors.forename: Tara
authors.initials: T
authors.lastname: Smith
authors.forename: Dayan B
authors.initials: DB
authors.lastname: Goodenowe
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016466:CHO Cells; D002103:Cadaverine / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000378:metabolism; D007052:Ibuprofen / Q000494:pharmacology*; D009369:Neoplasms / Q000517:prevention & control*; D010955:Plasmalogens / Q000494:pharmacology* / Q000502:physiology; D011700:Putrescine / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D027282:Fusion Regulatory Protein 1, Heavy Chain; D010955:Plasmalogens; D002103:Cadaverine; D011700:Putrescine; D007052:Ibuprofen
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