Differential effects of delivery of omega-3 fatty acids to human cancer cells by low-density lipoproteins versus albumin.
Clin Cancer Res
; 10(24): 8275-83, 2004 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-15623603
ABSTRACT
PURPOSE:
Omega-3 (n-3) fatty acids (FA) have been proposed to confer tumor-inhibitory properties. In vivo, dietary FA are delivered to tumor cells by two main routes low-density lipoproteins (LDL) and albumin complexes. High FA concentration in LDL and up-regulation of LDL receptors in tumor cells suggest that the LDL receptor pathway may be the major route for FA delivery. We compared effects of n-3FA delivered to human cancer cells by LDL and albumin. EXPERIMENTALDESIGN:
LDL was isolated from plasma of African Green monkeys fed diets enriched in fish oil (n-3 FA) or linoleic acid (n-6FA) and used to deliver FA to MCF-7 and PC3 cancer cells. Cell proliferation, apoptosis, and changes in global gene expression were monitored.RESULTS:
Both LDL and albumin were effective in delivering FA to tumor cells and modifying the composition of cell phospholipids. The molar ratio of 204 (n-6) to 205 (n-3) in phosphatidylcholine and phosphatidylethanolamine was profoundly decreased. Although cell phospholipids were similarly modified by LDL and albumin-delivered FA, effects on cell proliferation and on transcription were markedly different. LDL-delivered n-3 FA were more effective at inhibiting cell proliferation and inducing apoptosis. Expression microarray profiling showed that a significantly higher number of genes were regulated by LDL-delivered than albumin-delivered n-3 FA with little overlap between the two sets of genes.CONCLUSIONS:
These results show the importance of the LDL receptor pathway in activating molecular mechanisms responsible for the tumor inhibitory properties of n-3FA.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
/
Neoplasias da Mama
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Ácidos Graxos Ômega-3
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Sistemas de Liberação de Medicamentos
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Albuminas
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Lipoproteínas LDL
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article