Journal Article

Vitamin E inhibits cell proliferation and the activation of extracellular signal-regulated kinase during the promotion phase of lung tumorigenesis irrespective of antioxidative effect

Tomohiro Yano, Shoko Yajima, Kiyokazu Hagiwara, Itsumaro Kumadaki, Yoshihisa Yano, Shuzo Otani, Mikako Uchida and Tomio Ichikawa

in Carcinogenesis

Volume 21, issue 11, pages 2129-2133
Published in print November 2000 | ISSN: 0143-3334
Published online November 2000 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/21.11.2129
Vitamin E inhibits cell proliferation and the activation of extracellular signal-regulated kinase during the promotion phase of lung tumorigenesis irrespective of antioxidative effect

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We have already reported that the activation of extracellular signal-regulated kinase (Erk) is critical in the stimulation of cell proliferation during the promotion stage of urethane-induced lung tumorigenesis in mice. Also, we have found that vitamin E suppresses lung tumorigenesis by inhibiting cell proliferation at the promotion stage. However, it is still unclear whether this inhibitory effect at the promotion stage is based on the antioxidative effect of vitamin E or not. In order to address this question, we examined the inhibitory effect of α-tocopheryloxybutyric acid (TSE), an ether derivative of vitamin E that cannot act as an antioxidant in vivo, on cell proliferation and the activation of Erk during promotion of lung tumorigenesis. On day 30 after urethane injection (750 mg/kg, i.p.) in A/J mice, TSE or vitamin E at 100 μmol/kg, p.o. was administered. Twenty-four hours after the final administration, the mice were killed to analyze cell proliferation and related parameters. The labeling index of proliferating cell nuclear antigen (a marker of cell proliferation) and ornithine decarboxylase activity (a marker of the promotion stage in lungs) were attenuated by treatment with TSE or vitamin E. TSE or vitamin E treatment also inhibited urethane-induced activation of Erk and suppressed the activation of other essential members of the Erk cascade (Ras, Raf and Mek). These results suggest that vitamin E inhibits cell proliferation and activation of the Erk cascade during promotion of urethane-induced lung tumorigenesis in mice, independent of its antioxidative effect.

Keywords: EGFR, epidermal growth factor receptor; Erk, extracellular signal-regulated kinase; LI, labeling index; ODC, ornithine decarboxylase; PCNA, proliferating cell nuclear antigen; TSE, α-tocopheryloxybutyric acid.

Journal Article.  3390 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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