The suppression of ornithine decarboxylase expression and cell proliferation at the promotion stage of lung tumorigenesis in mice by alpha-tocopheryloxybutyric acid.
It is known that vitamin E inhibits tumor cell growth in vitro irrespective of its antioxidative effect. However, it is unclear whether the effect in vitro can be applied to the in vivo situation. In order to address this question, we estimated if alpha-tocopheryloxybutyric acid (TSE), a non-antioxidative vitamin E derivative in vivo, could inhibit cell proliferation during the tumorigenic process of lung in mice treated with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the most potent carcinogen among tobacco-specific nitrosamines. TSE administration suppressed the labeling index of the proliferating cell nuclear antigen, a marker of cell proliferation at a promotion phase of NNK-induced lung tumorigenesis in mice. Similarly, TSE administration inhibited the elevation of ornithine decarboxylase (ODC) activity and its mRNA at the promotion phase. Of four transcription factors contributing to ODC induction, the change in the level of the c-Myc/Max-consensus oligonucleotide complex was only proportional to the change in ODC mRNA level. These results suggest that vitamin E can inhibit cell proliferation linked with ODC induction at the promotion phase of lung tumorigenesis irrespective of its antioxidative effect and that modulation of the transactivation of the c-Myc/Max complex for the ODC gene by TSE in part contributes to the suppression of ODC induction.
Yano
T
T
Division of Applied Food Research, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan. yano@nih.go.jp
Yano
Y
Y
Yajima
S
S
Kumadaki
I
I
Ichikawa
T
T
Otani
S
S
Hagiwara
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D015197:Carcinogenicity Tests; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020868:Gene Silencing; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology*
D000970:Antineoplastic Agents; C113106:tocopheryloxybutyric acid; D014810:Vitamin E; D009955:Ornithine Decarboxylase