Differential Effects of Delivery of Omega-3 Fatty Acids to Human Cancer Cells by Low-Density Lipoproteins versus Albumin

• Published in: Clinical cancer research 2004-12, Vol.10 (24), p.8275-8283
• Main Authors: Edwards, Iris J, Berquin, Isabelle M, Sun, Haiguo, O'flaherty, Joseph T, Daniel, Larry W, Thomas, Michael J, Rudel, Lawrence L, Wykle, Robert L, Chen, Yong Q
• Format: Article
• Language: English
• Subjects: Albumins - administration & dosage; Animals; Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Proliferation - drug effects; Cercopithecus 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; Medical sciences; Oligonucleotide Array Sequence Analysis; Pharmacology. Drug treatments; Phosphatidylcholines - metabolism; Phosphatidylethanolamines - metabolism; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Triglycerides - metabolism; Tumor Cells, Cultured
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-04-1357

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.