Faculty Collaboration Database

Differential effects of delivery of omega-3 fatty acids to human cancer cells by low-density lipoproteins versus albumin. Clin Cancer Res 2004 Dec 15;10(24):8275-83

Date

12/30/2004

Pubmed ID

15623603

DOI

10.1158/1078-0432.CCR-04-1357

Scopus ID

2-s2.0-11144247920 (requires institutional sign-in at Scopus site)   33 Citations

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.

EXPERIMENTAL DESIGN: 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 20:4 (n-6) to 20:5 (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.

Author List

Edwards IJ, Berquin IM, Sun H, O'flaherty JT, Daniel LW, Thomas MJ, Rudel LL, Wykle RL, Chen YQ

Author

Michael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albumins
Animals
Apoptosis
Breast Neoplasms
Cell Proliferation
Cholesterol
Drug Delivery Systems
Fatty Acids, Omega-3
Female
Fish Oils
Gene Expression Profiling
Humans
Linoleic Acid
Lipoproteins, LDL
Male
Oligonucleotide Array Sequence Analysis
Phosphatidylcholines
Phosphatidylethanolamines
Prostatic Neoplasms
Triglycerides
Tumor Cells, Cultured