Chou Y.-CLin Y.-HLin P.-HTung Y.-CHo C.-TMIN-HSIUNG PAN2022-04-252022-04-25202102786915https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109442425&doi=10.1016%2fj.fct.2021.112380&partnerID=40&md5=a29a6e89cafc61a03ece0f21244ff6cbhttps://scholars.lib.ntu.edu.tw/handle/123456789/606147The 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 Ltd5-Demethylnobiletin (5-DMNB)Benzo[a]pyrene (BaP)Colon cancerXenobiotic-metabolizing enzymes5 demethylnobiletinantineoplastic agentbenzo[a]pyrenecytochrome P450 1B1glucuronosyltransferaseglutathione transferasetumor necrosis factorunclassified drug5-demethylnobiletinantiinflammatory agentCyp1b1 protein, mousedextran sulfateflavone derivativeanimal experimentanimal modelanimal tissueantineoplastic activityArticlebiotransformationcolon cancercolon carcinogenesiscontrolled studydetoxificationdrug determinationdrug effectdrug structureenzyme activitygene expressionmalemousenonhumanprotein expressionprotein functionupregulationanimalBagg albino mousecarcinogenesiscoloncolon tumorHep-G2 cell linehumanInstitute for Cancer Research mousemetabolismpathologyAnimalsAnti-Inflammatory AgentsAnticarcinogenic AgentsBenzo(a)pyreneCarcinogenesisColonColonic NeoplasmsCytochrome P-450 CYP1B1Dextran SulfateFlavonesGlucuronosyltransferaseGlutathione TransferaseHep G2 CellsHumansMaleMice, Inbred BALB CMice, Inbred ICR[SDGs]SDG3journal article10.1016/j.fct.2021.112380342167132-s2.0-85109442425