Inhibition of Activator Protein-1, NF-Kappa B, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid

Details

• Personal Author:
  Bowman LL ; Castranova, Vincent ; Ding M ; Feng RT ; Lu Y ; Qian Y
• Description:
  Chlorogenic acid, the ester of caffeic acid with quinic acid, is one of the most abundant polyphenols in the human diet. The antioxidant and anticarcinogenic properties of chlorogenic acid have been established in animal studies. However, little is known about the molecular mechanisms through which chlorogenic acid inhibits carcinogenesis. In this study, we found that chlorogenic acid inhibited the proliferation of A549 human cancer cells in vitro. The results of the soft agar assay indicated that chlorogenic acid suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of JB6 cells with chlorogenic acid blocked UVB- or TPA-induced transactivation of AP-1 and NF-kappaB over the same dose range. At low concentrations, chlorogenic acid decreased the phosphorylation of c-Jun NH2-terminal kinases, p38 kinase, and MAPK kinase 4 induced by UVB/12-O-tetradecanoylphorbol-13-acetate, yet higher doses were required to inhibit extracellular signal-regulated kinases. Chlorogenic acid also increased the enzymatic activities of glutathione S-transferases (GST) and NAD(P)H: quinone oxidoreductase. Further studies indicated that chlorogenic acid could stimulate the nuclear translocation of Nrf2 (NF-E2-related factor) as well as subsequent induction of GSTA1 antioxidant response element (ARE)-mediated GST activity. The phosphatidylinositol 3-kinase pathway might be involved in the activation of Nrf2 translocation. These results provide the first evidence that chlorogenic acid could protect against environmental carcinogen-induced carcinogenesis and suggest that the chemopreventive effects of chlorogenic acid may be through its up-regulation of cellular antioxidant enzymes and suppression of ROS-mediated NF-kappaB, AP-1, and MAPK activation. [Description provided by NIOSH]
• Subjects:
  Acids Animals Antioxidants Carcinogens Enzymes Laboratories Occupational Health Safety
• Keywords:
  Acidity Animal-studies Antioxidation Carcinogenesis Carcinogenicity In-vitro-studies Laboratory-animals
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  280
• Issue:
  30
• NIOSHTIC Number:
  nn:20028020
• Citation:
  J Biol Chem 2005 Jul; 280(30):27888-27895
• Contact Point Address:
  Pathology and Physiology Research Branch, Health Effect Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Rd., Morgantown, WV 26505
• Email:
  mid5@cdc.gov
• Federal Fiscal Year:
  2005
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4356c2fcbc1bfcc230b701f81b3b1274ea5c5fab8dd0565a1061cfd4217905825ed701b795827611a2d9c170997125b89ae6340f8c626d8f21567f19c0d8d52d
• Download URL:
  https://stacks.cdc.gov/view/cdc/189730/cdc_189730_DS1.pdf
• File Type:
  [PDF - 344.64 KB ]