title: Oroxylin A prevents inflammation-related tumor through down-regulation of inflammatory gene expression by inhibiting NF-κB signaling.
abstract: Increasing evidence suggests that inflammatory microenvironment plays a critical role at different stages of tumor development. However, the molecular mechanisms of the interaction between inflammation and proliferation of cancer cells remain poorly defined. Here we reported the inhibitory effects of oroxylin A on the inflammation-stimulated proliferation of tumor cells and delineated the mechanism of its action. The results indicated that treatment with oroxylin A inhibited NF-κB p65 nuclear translocation and phosphorylation of IκBα and IKKα/β in both human colon tumor HCT116 cells and human monocytes THP-1 cells. In addition, in THP-1 cells, oroxylin A significantly suppressed lipopolysaccharide (LPS)-induced secretion of prototypical proinflammatory cytokine IL-6 but not IL-1β, and it was confirmed at the transcription level. Moreover, oroxylin A inhibited the proliferation of HCT116 cells stimulated by LPS-induced THP-1 cells in co-culture microenvironment. In summary, oroxylin A modulated NF-κB signaling pathway involved in inflammation-induced cancer initiation and progression and therefore could be a potential cancer chemoprevention agent for inflammation-related cancer.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, People's Republic of, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Biqi
authors.initials: B
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Yunying
authors.initials: Y
authors.lastname: Sha
authors.forename: Binbin
authors.initials: B
authors.lastname: Zhu
authors.forename: Qi-Dong
authors.initials: QD
authors.lastname: You
authors.forename: Tianhua
authors.initials: T
authors.lastname: Yan
authors.forename: Qing-Long
authors.initials: QL
authors.lastname: Guo
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D045325:HCT116 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics
chemical_list: D005419:Flavonoids; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D051550:I-kappa B Kinase