https://scholars.lib.ntu.edu.tw/handle/123456789/606147
標題: | Dietary 5-demethylnobiletin modulates xenobiotic-metabolizing enzymes and ameliorates colon carcinogenesis in benzo[a]pyrene-induced mice | 作者: | Chou Y.-C Lin Y.-H Lin P.-H Tung Y.-C Ho C.-T MIN-HSIUNG PAN |
關鍵字: | 5-Demethylnobiletin (5-DMNB);Benzo[a]pyrene (BaP);Colon cancer;Xenobiotic-metabolizing enzymes;5 demethylnobiletin;antineoplastic agent;benzo[a]pyrene;cytochrome P450 1B1;glucuronosyltransferase;glutathione transferase;tumor necrosis factor;unclassified drug;5-demethylnobiletin;antiinflammatory agent;Cyp1b1 protein, mouse;dextran sulfate;flavone derivative;animal experiment;animal model;animal tissue;antineoplastic activity;Article;biotransformation;colon cancer;colon carcinogenesis;controlled study;detoxification;drug determination;drug effect;drug structure;enzyme activity;gene expression;male;mouse;nonhuman;protein expression;protein function;upregulation;animal;Bagg albino mouse;carcinogenesis;colon;colon tumor;Hep-G2 cell line;human;Institute for Cancer Research mouse;metabolism;pathology;Animals;Anti-Inflammatory Agents;Anticarcinogenic Agents;Benzo(a)pyrene;Carcinogenesis;Colon;Colonic Neoplasms;Cytochrome P-450 CYP1B1;Dextran Sulfate;Flavones;Glucuronosyltransferase;Glutathione Transferase;Hep G2 Cells;Humans;Male;Mice, Inbred BALB C;Mice, Inbred ICR | 公開日期: | 2021 | 卷: | 155 | 來源出版物: | Food and Chemical Toxicology | 摘要: | The intake of common polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), is strongly correlated to the initiation of colon cancer. BaP is a well-known pro-carcinogen that is metabolically activated by xenobiotic-metabolizing enzymes. Studies indicate that polymethoxyflavones, including 5-demethylnobiletin (5-DMNB), exhibit anti-inflammatory and anti-carcinogenic properties. However, the effects of 5-DMNB on xenobiotic-metabolizing enzymes and BaP-induced carcinogenesis remain unclear. The combination of BaP and a promoting agent—dextran sulfate sodium (DSS)—has been demonstrated to induce tumors in mouse models. Thus, this study aimed to determine the protective effect of 5-DMNB on carcinogen biotransformation and BaP/DSS-induced colon carcinogenesis. Our results showed that 5-DMNB had a substantial inhibitory effect on CYP1B1 induced by BaP and upregulated the detoxification enzymes UDP-glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs). Furthermore, subsequent analyses confirmed that the dietary administration of 5-DMNB markedly ameliorated tumor formation in BaP/DSS-treated mice. Exposure to BaP/DSS also significantly elevated TNF-α levels, and the administration of 5-DMNB reversed this increase. Taken together, we determined that 5-DMNB attenuates BaP/DSS-induced colon cancer through the regulation of inflammation and xenobiotic-metabolizing enzymes. These results indicate that 5-DMNB has significant potential as a novel chemopreventive agent for preventing carcinogen activation and inflammation-associated carcinogenesis. ? 2021 Elsevier Ltd |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109442425&doi=10.1016%2fj.fct.2021.112380&partnerID=40&md5=a29a6e89cafc61a03ece0f21244ff6cb https://scholars.lib.ntu.edu.tw/handle/123456789/606147 |
ISSN: | 02786915 | DOI: | 10.1016/j.fct.2021.112380 |
顯示於: | 食品科技研究所 |
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