Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens

Lipids in Health and Disease

Dayan B Goodenowe¹  Tara Smith¹  M Amin Khan¹  Paul L Wood² 

[1] R&D Dept., Phenomenome Discoveries Inc, 204-407 Downey Road, Saskatoon, SK, S7N 4L8 Canada;Dept. of Pharmacology, DeBusk College of Osteopathic Medicine, Lincoln Memorial University, 6965 Cumberland Gap Pkwy., Harrogate, TN 37752 USA

关键词: cancer chemoprevention;    ornithine decarboxylase;    diamine exporter;    cadaverine;    putrescine;    PPI-1011;    omega-3 fatty acids;    plasmalogens;    ibuprofen;    NRel-4;    CHO;   

Others  :  1212413
DOI  :  10.1186/1476-511X-10-214

 received in 2011-10-25, accepted in 2011-11-16,  发布年份 2011

【 摘 要 】

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.

【 授权许可】

   
2011 Wood et al; licensee BioMed Central Ltd.

【 图 表 】

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