4.6 Article

Oroxylin A Prevents Inflammation-Related Tumor Through Down-Regulation of Inflammatory Gene Expression by Inhibiting NF-κB Signaling

Journal

MOLECULAR CARCINOGENESIS
Volume 53, Issue 2, Pages 145-158

Publisher

WILEY
DOI: 10.1002/mc.21958

Keywords

oroxylin A; inflammatory cytokines; NF-kappa B; chemoprevention

Funding

  1. State Key Laboratory of Natural Medicines, China Pharmaceutical University [JKGZ201101]
  2. Natural Science Foundation of China [30801410, 30973556, 91029744, 81001452, 81173086, 81173087]
  3. Natural Science Foundation of Jiangsu Province, China [BK2009297, BK2010432]
  4. Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT-IRT1193]
  5. National Science & Technology Major Project [2012ZX09304-001]

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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-B p65 nuclear translocation and phosphorylation of IB and IKK/ 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-1, 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-B signaling pathway involved in inflammation-induced cancer initiation and progression and therefore could be a potential cancer chemoprevention agent for inflammation-related cancer. (c) 2012 Wiley Periodicals, Inc.

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