Dietary 5-demethylnobiletin inhibits cigarette carcinogen NNK-induced lung tumorigenesis in mice

文献类型： 外文期刊

第一作者： Song, Mingyue

作者： Song, Mingyue;Wu, Xian;Charoensinphon, Noppawat;Wang, Minqi;Zheng, Jinkai;Gao, Zili;Xu, Fei;Li, Zhengze;Li, Fang;Zhou, Jiazhi;Xiao, Hang;Zheng, Jinkai

作者机构：

期刊名称：FOOD & FUNCTION （ 影响因子：5.396； 五年影响因子：5.534 ）

ISSN：

年卷期：

页码：

收录情况： SCI

摘要： 5-Demethylnobiletin (5DN) is a unique citrus flavonoid with various beneficial bioactivities. In this study, we determined the inhibitory effects of 5DN and its two major metabolites in the 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis mouse model as well as in human and mouse lung cancer cell models. In NNK-treated female A/J mice, dietary administration of 5DN (0.025% or 0.05% w/w in the diet) significantly decreased both lung tumor multiplicity and tumor volume. Immunohistochemical analysis showed strong anti-proliferative effects of 5DN in lung tumors. Two major metabolites of 5DN, named 5,3'-didemethylnobiletin (M1) and 5,4'-didemethylnobiletin (M2), were found in the lung tissue of 5DN-fed mice. Cell culture studies demonstrated that 5DN, M1 and M2 significantly inhibited the growth of human and mouse lung cancer cells by causing cell cycle arrest, inducing apoptosis and modulating key signaling proteins related to cell proliferation and cell death. Interestingly, the metabolites of 5DN, especially M1 produced much stronger inhibitory effects on both human and mouse lung cancer cells than those produced by 5DN itself. Our results demonstrated that dietary administration of 5DN significantly inhibited NNK-induced tumorigenesis in mice, and this effect may be partially associated with the metabolites of 5DN in lung tissues.

分类号： TS2

  • 相关文献
作者其他论文 更多>>

微信小程序