Berry Extracts Inhibit Activating Protein 1 (AP-1) Function and Cell Transformation by Perturbing the Mitogenic Signaling Pathway

Details

• Personal Author:
  Bowman LL ; Castranova, Vincent ; Ding M ; Feng R ; Lu Y
• Description:
  Berry extracts, such as blackberry (BB) and strawberry (SB), are natural rich sources of bioflavonoids and phenolic compounds. These compounds are commonly known as potential cancer chemopreventive agents. Early studies indicated that berry-extracts exhibit antioxidant and antitumorogenic activities in vitro and in vivo. The molecular mechanisms of their actions remain unclear. In this study, we investigated the effects of berry extracts on cancer cell growth and cell transformation induced by 12-0-tetradecanoylphorbol13-acetate (TPA). The underlying mechanisms of chemoprevention, including suppression of oxidative DNA damage and blockage of the transactivatlon of activator protein 1 (AP1) as well as associated signal transduction pathways were also explored. At the cellular level, the berry extracts inhibited the attachment and growth of lung-cancer cells. Results of the soft agar assay indicated that both BB and SB decreased TPA-induced neoplastic transformation of JB6 P+ cells in a dose-dependent manner. Pretreatment of A549 cells with BB or SB resulted in an inhibition of 8-hydroxy-2'-deoxyguanosine formation induced by UVB irradiation. Pretreatment of JB6 cells with berry extracts also resulted in an inhibition of UVB- or TPA-induced AP-l transactivation. BB or SB treatment of JEG cells inhibited the phosphorylation of extracellular signal-regulated kinases (ERKs) and c-Jun NH(2)-terminal kinases (JNKs), but not p38 kinase. Together, these results suggest that BB and SB exhibit potent chemopreventive activity. The possible mechanism by which BB and SB suppress JB6 cell transformation appears to involve the inhibition of AP-l transactivation as well as its upstream MAPK family members, including ERKs and JNKs. Description provided by NIOSH
• Subjects:
  • Carcinogens
  • Free Radicals
  • Lung
  • Lung Diseases
  • Neoplasms
  • Occupational Health
  • Phenol
  • Respiratory System
  • Respiratory Tract Diseases
  • Safety
• Keywords:
  • Cell-transformation
  • Phenols
  • Phenolic-compounds
  • Cancer
  • Free-radicals
  • Lung-cancer
  • Pulmonary-system-disorders
  • Respiratory-system-disorders
  • Carcinogenesis
  • Carcinogenicity
  More +
• Document Type:
  Text
• Genre:
  Abstract or Summary ; Proceedings
• Place as Subject:
  Arizona ; OSHA Region 3 ; OSHA Region 9 ; Pennsylvania ; 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:
  12
• NIOSHTIC Number:
  nn:20032298
• Citation:
  Proceedings of the American Association for Cancer Research (AACR) 2nd Conference on Frontiers in Cancer Prevention Research, October 26-30, 2003. Phoenix, Arizona. Philadelphia, PA: American Association for Cancer Research, 2003 Nov; 12(Suppl):1299s
• Federal Fiscal Year:
  2004
• Peer Reviewed:
  False
• Source Full Name:
  Proceedings of the American Association for Cancer Research (AACR) 2nd Conference on Frontiers in Cancer Prevention Research, October 26-30, 2003, Phoenix, Arizona
• Supplement:
  Suppl
• Download URL:
  https://stacks.cdc.gov/view/cdc/186323/cdc_186323_DS1.pdf
• File Type:
  [PDF - 297.04 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:466e37d34421337d2c1d22f8ed6bc0bfbd8b013b2dc5f2ad0b197599f1de7ef2a98798e853f59b561535a35c37b92424baac22a14bacc8f124b967f1e7f044bf