Black Raspberry Extracts Inhibit Benzo(a)pyrene Diol-Epoxide-Induced Activator Protein 1 Activation and VEGF Transcription by Targeting the Phosphotidylinositol 3-Kinase/Akt Pathway

Details

• Personal Author:
  Aziz R ; Bowman L ; Ding M ; Huang CS ; Li JX ; Song L ; Sonter GD ; Tong QS ; Zhang DY
• Description:
  Previous studies have shown that freeze-dried black raspberry extract fractions inhibit benzo(a)pyrene [B(a)P]-induced transformation of Syrian hamster embryo cells and benzo(a)pyrene diol-epoxide [B(a)PDE]-induced activator protein-1 (AP-1) activity in mouse epidermal Cl 41 cells. The phosphotidylinositol 3-kinase (PI-3K)/Akt pathway is critical for B(a)PDE-induced AP-1 activation in mouse epidermal Cl 41 cells. In the present study, we determined the potential involvement of PI-3K and its downstream kinases on the inhibition of AP-1 activation by black raspberry fractions, RO-FOO3, RO-FOO4, RO-ME, and RO-DM. In addition, we investigated the effects of these fractions on the expression of the AP-1 target genes, vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS). Pretreatment of Cl 41 cells with fractions RO-F003 and RO-ME reduced activation of AP-1 and the expression of VEGF, but not iNOS. In contrast, fractions RO-F004 and RO-DM had no effect on AP-1 activation or the expression of either VEGF or iNOS. Consistent with inhibition of AP-1 activation, the RO-ME fraction markedly inhibited activation of PI-3K, Akt, and p70 S6 kinase (p70(S6k)). In addition, overexpression of the dominant negative PI-3K mutant delta p85 reduced the induction of VEGF by B(a)PDE. It is likely that the inhibitory effects of fractions RO-FOO3 and RO-ME on B(a)PDE-induced AP-1 activation and VEGF expression are mediated by inhibition of the PI-3K/Akt pathway. In view of the important roles of AP-1 and VEGF in tumor development, one mechanism for the chemopreventive activity of black raspberries may be inhibition of the PI-3K/Akt/AP-1/VEGF pathway. [Description provided by NIOSH]
• Subjects:
  Animals Cells, Cultured Genetics Laboratories Neoplasms Occupational Health Safety
• Keywords:
  Animal-studies Author Keywords: PAHs Berries Cancer Cell-cultures Cell-transformation Chemoprevention Gene Expression Genes Laboratory-animals Signal Transduction Tumors

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• ISSN:
  0008-5472
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  New York ; Ohio ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; 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:
  66
• Issue:
  1
• NIOSHTIC Number:
  nn:20029332
• Citation:
  Cancer Res 2006 Jan; 66(1):581-587
• Contact Point Address:
  Chuanshu Huang, Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987
• Email:
  chuanshu@env.med.nyu.edu
• CAS Registry Number:
  Benzo[a]pyrene (CAS RN 50-32-8)
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Cancer Research
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:33b22de4c2154be4decd7a788a1bd889f4079514bbc357b4282d448a345e911fa82db644f3abf32f9dde3413dc2c6531c094ff8e2b3fdd5f7b48a1bb1d59f805
• Download URL:
  https://stacks.cdc.gov/view/cdc/190338/cdc_190338_DS1.pdf
• File Type:
  [PDF - 388.95 KB ]