title: Quercetin suppresses cytochrome P450 mediated ROS generation and NFκB activation to inhibit the development of 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinomas.
abstract: Increased production of reactive oxygen species (ROS) has long been recognized to play a pivotal role in carcinogenesis. Quercetin, a naturally occurring dietary flavonoid is known for its ROS scavenging properties. The present study was designed to investigate the chemopreventive and chemotherapeutic effects of quercetin based on cytochrome P450 (CYP) mediated ROS generation, ROS-induced cellular damage and activation of the NFκB signalling circuit during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. Administration of quercetin inhibited the development of DMBA-induced HBP carcinomas by impairing CYP-mediated ROS production via downregulation of the expression of CYP1A1 and CYP1B1, and upregulation of antioxidant defences. Attenuation of ROS generation by quercetin in turn abrogated NFκB signalling by preventing the phosphorylation and degradation of IκB, nuclear translocation of NFκB and transactivation of its target genes associated with cell proliferation and apoptosis evasion. Thus dietary flavonoids such as quercetin that can block ROS generation and inhibit the redox regulated transcription factor NFκB, by virtue of their antioxidant potential are promising candidates for future antioxidant-based anticancer regimens.
authors: Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India.
authors: Ramamurthi Vidya
authors: RV
authors: Priyadarsini
authors: Siddavaram
authors: S
authors: Nagini
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D002610:Cheek; D006224:Cricetinae; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D003839:Deoxyadenosines / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008647:Mesocricetus; D051379:Mice; D009062:Mouth Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016328:NF-kappa B / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C436623:8-hydroxy-2'-deoxyadenosine; D000975:Antioxidants; D065607:Cytochrome P-450 Enzyme Inhibitors; D003839:Deoxyadenosines; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D002374:Catalase; D013482:Superoxide Dismutase