Abstract |
The multi-functional apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) DNA repair and redox signaling protein has been shown to have a role in cancer growth and survival, however, little has been investigated concerning its role in inflammation. In this study, an APE1 redox-specific inhibitor ( E3330) was used in lypopolysaccharide (LPS)-stimulated macrophages (RAW264.7). E3330 clearly suppressed secretion of inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL-6) and IL-12 and inflammatory mediators nitric oxide (NO) as well as prostaglandin E(2) ( PGE(2)) from the LPS-stimulated RAW264.7 cells. These data were supported by the down-regulation of the LPS-dependent expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) genes in the RAW264.7 cells. The effects of E3330 were mediated by the inhibition of transcription factors nuclear factor-κB (NF-κB) and activator protein 1 (AP-1) in the LPS-stimulated macrophages, both known targets of APE1. In conclusion, pharmacological inhibition of APE1 by E3330 suppresses inflammatory response in activated macrophages and can be considered as a novel therapeutic strategy for the inhibition of tumor-associated macrophages.
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Authors | Andrej Jedinak, Shailesh Dudhgaonkar, Mark R Kelley, Daniel Sliva |
Journal | Anticancer research
(Anticancer Res)
Vol. 31
Issue 2
Pg. 379-85
(Feb 2011)
ISSN: 1791-7530 [Electronic] Greece |
PMID | 21378315
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Benzoquinones
- Lipopolysaccharides
- NF-kappa B
- Propionates
- Transcription Factor AP-1
- Tumor Necrosis Factor-alpha
- E 3330
- Nitric Oxide
- Nitric Oxide Synthase Type II
- Nos2 protein, mouse
- Ptgs2 protein, mouse
- Cyclooxygenase 2
- Apex1 protein, mouse
- DNA-(Apurinic or Apyrimidinic Site) Lyase
- Dinoprostone
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
- Benzoquinones
(pharmacology)
- Cells, Cultured
- Cyclooxygenase 2
(biosynthesis)
- DNA-(Apurinic or Apyrimidinic Site) Lyase
(antagonists & inhibitors, immunology, metabolism)
- Dinoprostone
(immunology, metabolism)
- Lipopolysaccharides
(pharmacology)
- Macrophages
(drug effects, enzymology, immunology)
- Mice
- NF-kappa B
(immunology, metabolism)
- Nitric Oxide
(immunology, metabolism)
- Nitric Oxide Synthase Type II
(biosynthesis)
- Oxidation-Reduction
- Propionates
(pharmacology)
- Signal Transduction
- Transcription Factor AP-1
(immunology, metabolism)
- Tumor Necrosis Factor-alpha
(biosynthesis)
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