Suppression of tumor cell growth both in nude mice and in culture by n-3 polyunsaturated fatty acids: mediation through cyclooxygenase-independent pathways.
Dietary n-3 polyunsaturated fatty acids (PUFAs), as compared with n-6 PUFAs, suppress cellular production of prostaglandins and tumor cell growth both in vitro and in vivo. However, the mechanism by which n-3 PUFAs suppress tumor growth is not understood. We investigated whether the suppression of tumor cell growth by dietary n-3 PUFAs is mediated through inhibition of cyclooxygenase (COX). A colon tumor cell line, HCT-116, that does not express COX was stably transfected with the constitutively expressed COX-1 or the inducible COX-2 cDNA using a retroviral transfection and infection system. Athymic nude mice transplanted with the cells expressing enzymatically active COX were fed isocaloric diets containing either safflower oil or fish oil for 2 weeks before the start of the experiment and for an additional 21 days after transplantation. Both tumor volume and tumor burden (tumor volume/body weight) were significantly reduced in mice fed the fish oil diet as compared with safflower oil-fed mice. This reduction occurred even in control mice that received injections with cells infected with the retroviral vector without COX-1 or COX-2 cDNA. The growth of tumor cells expressing COX was not different from the growth of those transfected with the vector alone in the nude mice and in soft agar. N-3 PUFAs, as compared with linoleic acid, also inhibited the growth of these cells in culture. This growth inhibition by n-3 PUFAs was not affected by COX-1 or COX-2 overexpression. Contrary to general belief, these results indicate that the suppression of tumor growth by dietary n-3 PUFAs is mediated through COX-independent pathways.
Pennington, Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA.
M D
MD
Boudreau
K H
KH
Sohn
S H
SH
Rhee
S W
SW
Lee
J D
JD
Hunt
D H
DH
Hwang
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D018076:DNA, Complementary / Q000235:genetics; D004032:Diet; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D019787:Linoleic Acid / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012450:Safflower Oil / Q000494:pharmacology; D014162:Transfection; D014280:Triglycerides / Q000494:pharmacology*
D018076:DNA, Complementary; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D006131:Growth Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D014280:Triglycerides; C077446:Pikasol; D012450:Safflower Oil; D019787:Linoleic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse