Differential effects of delivery of omega-3 fatty acids to human cancer cells by low-density lipoproteins versus albumin.

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.

• Authors: Iris J Edwards, Isabelle M Berquin, Haiguo Sun, Joseph T O'flaherty, Larry W Daniel, Michael J Thomas, Lawrence L Rudel, Robert L Wykle, Yong Q Chen
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 24 Pg. 8275-83 (Dec 15 2004) ISSN: 1078-0432 [Print] United States
• PMID: 15623603 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Albumins
• Fatty Acids, Omega-3
• Fish Oils
• Lipoproteins, LDL
• Phosphatidylcholines
• Phosphatidylethanolamines
• Triglycerides
• phosphatidylethanolamine
• Cholesterol
• Linoleic Acid

Topics

• Albumins (administration & dosage)
• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (metabolism, pathology)
• Cell Proliferation (drug effects)
• Chlorocebus aethiops
• Cholesterol (metabolism)
• Drug Delivery Systems
• Fatty Acids, Omega-3 (administration & dosage)
• Female
• Fish Oils (administration & dosage)
• Gene Expression Profiling
• Humans
• Linoleic Acid (administration & dosage)
• Lipoproteins, LDL (administration & dosage)
• Male
• Oligonucleotide Array Sequence Analysis
• Phosphatidylcholines (metabolism)
• Phosphatidylethanolamines (metabolism)
• Prostatic Neoplasms (metabolism, pathology)
• Triglycerides (metabolism)
• Tumor Cells, Cultured