Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 28, Issue 1, Pages 764-772Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2015.08.003
Keywords
Dihydrotanshinone I; Nuclear factor-kappa B (NF-kappa B); I kappa B alpha; Inflammation; Cancer
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Funding
- National Natural Science Foundation of China [81360496, 81160250]
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The nuclear factor-kappa B (NF-kappa B) transcription factors control many physiological processes including inflammation, immunity, apoptosis, and angiogenesis. We identified dihydrotanshinone I as an inhibitor of NF-kappa B activation through our research on Salvia miltiorrhiza Bunge. In this study, we found that dihydrotanshinone I significantly inhibited the expression of NF-kappa B reporter gene induced by TNF-alpha in a dose-dependent manner. And dihydrotanshinone I also inhibited TNF-alpha induced phosphorylation and degradation of I kappa B alpha, phosphorylation and nuclear translocation of p65. Furthermore, pretreatment of cells with this compound prevented the TNF-alpha-induced expression of NF-kappa B target genes, such as anti-apoptosis (cIAP-1 and FLIP), proliferation (COX-2), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-alpha, IL-6, and MCPI). We also demonstrated that dihydrotanshinone I potentiated TNF-alpha-induced apoptosis. Moreover, dihydrotanshinone I significantly impaired activation of extracellular signal-regulated kinase 1/2 (ERK1/2), p38 and stress-activated protein kinase/c-Jun NH2-terminal kinase (JNK/SAPK). In vivo studies demonstrated that dihydrotanshinone I suppressed the growth of HeLa cells in a xenograft tumor model, which could be correlated with its modulation of TNF-alpha production. Taken together, dihydrotanshinone I could be a valuable candidate for the intervention of NF-kappa B-dependent pathological conditions such as inflammation and cancer. (C) 2015 Elsevier B.V. All rights reserved.
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