It has been well known that vitamin E inhibits tumor cell growth in vitro irrespective of its antioxidative effect. We synthesized a non-antixoidative vitamin E derivative in vivo, α-tocopheryloxybutyric acid (TE) and checked the anti-carcinogenic effect of TE in vivo as well as in vitro. TE inhibited in vivo cell proliferation during carcinogenic process of lung in mice treated with NNK, the most potent carcinogen among tabacco-specific nitrosamines. This inhibitory effect was in part based on the inactivation of Ras signaling and the suppression of ornithine decarboxylase induction. As well, TE inhibited in vitro breast cancer cell growth and induced apoptosis in the cell due to the inactivation of survival signal (ErbB2-Akt pathway) and activation of apoptotic signal (p38 signal pathway). Collectively, a strategy of cancer therapy and prevention based on non-antioxidative effect of vitamin E is promising.
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