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: Jing Yao, Rong Hu, Jie Sun, Biqi Lin, Li Zhao, Yunying Sha, Binbin Zhu, Qi-Dong You, Tianhua Yan, Qing-Long Guo
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 53 Issue 2 Pg. 145-58 (Feb 2014) ISSN: 1098-2744 [Electronic] United States
• PMID: 22949302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 Wiley Periodicals, Inc.

Chemical References

• Flavonoids
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• 5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
• I-kappa B Kinase

Topics

• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects, genetics)
• Down-Regulation (drug effects)
• Flavonoids (pharmacology)
• Gene Expression (drug effects, genetics)
• HCT116 Cells
• Humans
• I-kappa B Kinase (genetics)
• Inflammation (drug therapy, genetics, metabolism)
• Interleukin-1beta (genetics)
• Interleukin-6 (genetics)
• NF-kappa B (antagonists & inhibitors, genetics)
• Phosphorylation (drug effects)
• Signal Transduction (drug effects, genetics)