Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens
<p>Abstract</p> <p>Background</p> <p>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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-11-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://www.lipidworld.com/content/10/1/214 |
| _version_ | 1831728983718232064 |
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| author | Wood Paul L Khan M Smith Tara Goodenowe Dayan B |
| author_facet | Wood Paul L Khan M Smith Tara Goodenowe Dayan B |
| author_sort | Wood Paul L |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p> |
| first_indexed | 2024-12-21T07:01:17Z |
| format | Article |
| id | doaj.art-ccae4fb67654433983e80d9146f57d4a |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-21T07:01:17Z |
| publishDate | 2011-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-ccae4fb67654433983e80d9146f57d4a2022-12-21T19:12:13ZengBMCLipids in Health and Disease1476-511X2011-11-0110121410.1186/1476-511X-10-214Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogensWood Paul LKhan MSmith TaraGoodenowe Dayan B<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>http://www.lipidworld.com/content/10/1/214CHONRel-4ibuprofenplasmalogensomega-3 fatty acidsPPI-1011putrescinecadaverinediamine exporterornithine decarboxylasecancer chemoprevention |
| spellingShingle | Wood Paul L Khan M Smith Tara Goodenowe Dayan B Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens Lipids in Health and Disease CHO NRel-4 ibuprofen plasmalogens omega-3 fatty acids PPI-1011 putrescine cadaverine diamine exporter ornithine decarboxylase cancer chemoprevention |
| title | Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens |
| title_full | Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens |
| title_fullStr | Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens |
| title_full_unstemmed | Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens |
| title_short | Cellular diamine levels in cancer chemoprevention: modulation by ibuprofen and membrane plasmalogens |
| title_sort | cellular diamine levels in cancer chemoprevention modulation by ibuprofen and membrane plasmalogens |
| topic | CHO NRel-4 ibuprofen plasmalogens omega-3 fatty acids PPI-1011 putrescine cadaverine diamine exporter ornithine decarboxylase cancer chemoprevention |
| url | http://www.lipidworld.com/content/10/1/214 |
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