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


METHODS
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.
Edwards
Iris J
IJ
Department of Pathology, Wake Forest University, School of Medicine, Winston-Salem, North Carolina 27157, USA. iedwards@wfubmc.edu
Berquin
Isabelle M
IM
Sun
Haiguo
H
O'flaherty
Joseph T
JT
Daniel
Larry W
LW
Thomas
Michael J
MJ
Rudel
Lawrence L
LL
Wykle
Robert L
RL
Chen
Yong Q
YQ
D000418:Albumins / Q000008:administration & dosage*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000378:metabolism; D016503:Drug Delivery Systems; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010713:Phosphatidylcholines / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000418:Albumins; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D014280:Triglycerides; C483858:phosphatidylethanolamine; D002784:Cholesterol; D019787:Linoleic Acid