Jump to main content
Jump to site search

Issue 3, 2017
Previous Article Next Article

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

Author affiliations

Abstract

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.

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

Back to tab navigation

Publication details

The article was received on 18 Sep 2016, accepted on 25 Jan 2017 and first published on 26 Jan 2017


Article type: Paper
DOI: 10.1039/C6FO01367H
Citation: Food Funct., 2017,8, 954-963
  •   Request permissions

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

    M. Song, X. Wu, N. Charoensinphon, M. Wang, J. Zheng, Z. Gao, F. Xu, Z. Li, F. Li, J. Zhou and H. Xiao, Food Funct., 2017, 8, 954
    DOI: 10.1039/C6FO01367H

Search articles by author

Spotlight

Advertisements