ReferenceID 4399
Dietary 5-demethylnobiletin modulates xenobiotic-metabolizing enzymes and ameliorates colon carcinogenesis in benzo[a]pyrene-induced mice
Food Chem Toxicol
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
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Record Fields
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- Reference Id
- 4399
- Evidence Id
- 20989
- Core Evidence Id
- 20989
- Source Reference Id
- 2088
- Herb2 Reference Id
- HBREF002885
- Subject Paper Key
- HBIN011511_34216713
- Pubmed Id
- 34216713
- Doi
- 10.1016/j.fct.2021.112380
- Paper Title
- Dietary 5-demethylnobiletin modulates xenobiotic-metabolizing enzymes and ameliorates colon carcinogenesis in benzo[a]pyrene-induced mice
- Paper Abstract
- 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-alpha 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.
- Journal
- Food Chem Toxicol
- Publish Year
- 2021
- Experiment Subject
- mouse
- Experiment Type
- Animal Experiment
- Phenotype Related
- Tumors; Colon Cancer; Tumor
- Paper Title Cn
- Paper Title En
- Dietary 5-demethylnobiletin modulates xenobiotic-metabolizing enzymes and ameliorates colon carcinogenesis in benzo[a]pyrene-induced mice
- Bilingual Status
- semi_complete