High oleic acid oil suppresses lung tumorigenesis in mice through the modulation of extracellular signal-regulated kinase cascade.
This study was undertaken to estimate the effect of dietary high oleic acid oil (OA) on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in mice. Diet containing 10% oil was fed to mice through experimental periods. On day 30 after NNK injection (100 mg/kg body weight, i.p.), the treatment increased the level of prostaglandin E2 (PGE2) as well as proliferating cell nuclear antigen, a marker of cell proliferation in a high linoleic acid oil (LA)-fed group but not in an OA-fed group. The NNK treatment also induced the activation of an extracellular signal-regulated kinase (Erk) cascade (Erk, Mek and Raf-1) in an LA-fed group. On the other hand, OA feeding abolished the NNK-induced activation of the Erk cascade. In conjugation with these events, OA feeding reduced lung tumor incidence and tumor multiplicity (percentage of mice with tumors) in mice compared with LA feeding at the 20th experimental week. These results suggest that OA suppresses lung tumorigenesis and that this suppression is correlated with the inhibition of PGE2 production and inactivation of the Erk cascade.
Yamaki
Tatsuya
T
College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan.
Yano
Tomohiro
T
Satoh
Haruna
H
Endo
Tatsuo
T
Matsuyama
Chinami
C
Kumagai
Hitomi
H
Miyahara
Mitsuyoshi
M
Sakurai
Hidetoshi
H
Pokorny
Jan
J
Shin
Sung Jae
SJ
Hagiwara
Kiyokazu
K
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism / Q000517:prevention & control*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008805:Mice, Inbred A; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009602:Nitrosamines; D019301:Oleic Acid / Q000737:chemistry / Q000494:pharmacology*; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D009602:Nitrosamines; D010938:Plant Oils; D018809:Proliferating Cell Nuclear Antigen; D019301:Oleic Acid; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D015232:Dinoprostone