Blackberry Extracts Inhibit Activating Protein 1 Activation and Cell Transformation by Perturbing the Mitogenic Signaling Pathway

Nutr Cancer. 2004;50(1):80-9. doi: 10.1207/s15327914nc5001_11.

Abstract

Blackberries are natural rich sources of bioflavonoids and phenolic compounds that are commonly known as potential chemopreventive agents. Here, we investigated the effects of fresh blackberry extracts on proliferation of cancer cells and neoplastic transformation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as well as the underlying mechanisms of signal transduction pathways. Using electron spin resonance, we found that blackberry extract is an effective scavenger of free radicals, including hydroxyl and superoxide radicals. Blackberry extract inhibited the proliferation of a human lung cancer cell line, A549. Pretreatment of A549 cells with blackberry extract resulted in an inhibition of 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation induced by ultraviolet B (UVB) irradiation. Blackberry extract decreased TPA-induced neoplastic transformation of JB6 P+ cells. Pretreatment of JB6 cells with blackberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 transactivation. Furthermore, blackberry extract also blocked UVB- or TPA-induced phosphorylation of ERKs and JNKs, but not p38 kinase. Overall, these results indicated that an extract from fresh blackberry may inhibit tumor promoter-induced carcinogenesis and associated cell signaling, and suggest that the chemopreventive effects of fresh blackberry may be through its antioxidant properties by blocking reactive oxygen species-mediated AP-1 and mitogen-activated protein kinase activation.

MeSH terms

  • Antioxidants / pharmacology*
  • Cell Division / drug effects
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / drug effects*
  • Electron Spin Resonance Spectroscopy
  • Free Radical Scavengers
  • Fruit / chemistry*
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / drug effects
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species
  • Signal Transduction
  • Tetradecanoylphorbol Acetate / toxicity
  • Transcription Factor AP-1 / antagonists & inhibitors*
  • Transcription Factor AP-1 / metabolism

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Plant Extracts
  • Reactive Oxygen Species
  • Transcription Factor AP-1
  • Mitogen-Activated Protein Kinase Kinases
  • Tetradecanoylphorbol Acetate