Opposing effects of n-6 and n-3 polyunsaturated fatty acids on pancreatic cancer growth.
OBJECTIVE
Epidemiologic studies suggest that fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), possesses antitumor activity, whereas n-6 PUFAs may stimulate the development of cancers. The aim of this study was to evaluate the effects of n-6 and n-3 PUFAs on the growth of pancreatic cancer.


METHODS
The n-6 PUFA arachidonic acid (AA) stimulated the growth of cyclooxygenase (COX) 2 positive human pancreatic cancer (PaCa) cells, which was mediated by COX-2 generated prostaglandin E2 (PGE2) binding to EP2 and EP4 receptors. In contrast, the n-3 PUFA eicosapentaenoic acid decreased the growth of COX-2-positive and COX-2-negative PaCa cells. The COX-2-dependent mechanism of eicosapentaenoic acid was mediated by binding of PGE3 to EP2 and EP4 receptors. Dietary intake of n-3 PUFAs decreased the growth of pancreatic cancers in a xenograft model, which was accompanied by a decrease of PGE2 and an increase of PGE3 in the tumors.


CONCLUSIONS
Our studies provide evidence that n-3 PUFAs possess antitumor activities, whereas n-6 PUFAs stimulate pancreatic tumor growth. The opposite effects of n-3 and n-6 PUFAs are mediated by the formation of different prostaglandin species. n-3 PUFAs may prove beneficial as monotherapy or combination therapy with standard chemotherapeutic agents in pancreatic cancer patients.
Funahashi
Hitoshi
H
Hirshberg Laboratories for Pancreatic Cancer Research, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
Satake
Makoto
M
Hasan
Sascha
S
Sawai
Hirozumi
H
Newman
Robert A
RA
Reber
Howard A
HA
Hines
Oscar J
OJ
Eibl
Guido
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D023421:Models, Animal; D010190:Pancreatic Neoplasms / Q000196:embryology / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000032:analysis; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D011453:Prostaglandins; D012334:RNA, Neoplasm; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3