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Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells

  • Akira Murakami und Hajime Ohigashi
Veröffentlicht/Copyright: 11. April 2006
Biological Chemistry
Aus der Zeitschrift Band 387 Heft 4

Abstract

Active inflammatory leukocytes are a major endogenous source of reactive oxygen and nitrogen oxide species (RONS). We have recently established novel bioassay systems, in which either phorbol ester-stimulated, differentiated HL-60 human leukemia cells or lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophages were co-cultured with AS52 Chinese hamster ovary cells. Extensive screening of extracts from Asian vegetables and fruits led to the identification of 1′-acetoxychavicol acetate (ACA), auraptene, nobiletin, and zerumbone, all of which were found to be highly anti-mutagenic in the above co-culture systems. Pretreatment of RAW264.7 macrophages with LPS led to the activation of mitogen-activated protein kinases (MAPKs) and Akt, together with the degradation of IκB-α protein, and the resultant activation of the AP-1, NF-κB, and CREB transcription factors. ACA abrogated ERK1/2 and JNK1/2, but not p38 activation, as well as the activation and transcriptional activation of NF-κB and CREB, whereas nobiletin allowed phosphorylation of these MAPKs, while it suppressed AP-1, NF-κB, and CREB activation. Interestingly, zerumbone did not have any effects on the latter transcription factors, although it did attenuate iNOS mRNA expression. In addition, auraptene suppressed iNOS protein production, but not mRNA expression, implying that it targets the translation step. Our model systems may be useful for identifying potentially anti-carcinogenic inhibitors of RONS generation.

Keywords: chemoprevention; co-culture; macrophage; mutagenesis; nitric oxide; phytochemicals; superoxide
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Corresponding author

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Published Online: 2006-04-11
Published in Print: 2006-04-01

©2006 by Walter de Gruyter Berlin New York

Artikel in diesem Heft

  1. Highlight: chronic oxidative stress and cancer
  2. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
  3. Does Helicobacter pylori cause gastric cancer via oxidative stress?
  4. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis
  5. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
  6. Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
  7. Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells
  8. Evidence for attenuated cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine removal in cancer patients
  9. The roles of ATP in the dynamics of the actin filaments of the cytoskeleton
  10. Chiral distinction between the enantiomers of bicyclic alcohols by UDP-glucuronosyltransferases 2B7 and 2B17
  11. A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms
  12. Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function
  13. Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue
  14. BID, an interaction partner of protein kinase CK2α
  15. Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity
  16. Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling
  17. Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
  18. A fluorescence assay for rapid detection of ligand binding affinity to HIV-1 gp41
https://doi.org/10.1515/BC.2006.052
Schlagwörter für diesen Artikel
chemoprevention; co-culture; macrophage; mutagenesis; nitric oxide; phytochemicals; superoxide

Artikel in diesem Heft

  1. Highlight: chronic oxidative stress and cancer
  2. Risk factors and mechanisms of hepatocarcinogenesis with special emphasis on alcohol and oxidative stress
  3. Does Helicobacter pylori cause gastric cancer via oxidative stress?
  4. Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis
  5. Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids
  6. Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice
  7. Cancer-preventive anti-oxidants that attenuate free radical generation by inflammatory cells
  8. Evidence for attenuated cellular 8-oxo-7,8-dihydro-2′-deoxyguanosine removal in cancer patients
  9. The roles of ATP in the dynamics of the actin filaments of the cytoskeleton
  10. Chiral distinction between the enantiomers of bicyclic alcohols by UDP-glucuronosyltransferases 2B7 and 2B17
  11. A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms
  12. Role of the kinin B1 receptor in insulin homeostasis and pancreatic islet function
  13. Comparative proteomic analysis of neoplastic and non-neoplastic germ cell tissue
  14. BID, an interaction partner of protein kinase CK2α
  15. Monomeric and dimeric GDF-5 show equal type I receptor binding and oligomerization capability and have the same biological activity
  16. Novel ketomethylene inhibitors of angiotensin I-converting enzyme (ACE): inhibition and molecular modelling
  17. Identification of trypsin I as a candidate for influenza A virus and Sendai virus envelope glycoprotein processing protease in rat brain
  18. A fluorescence assay for rapid detection of ligand binding affinity to HIV-1 gp41
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