Differential effects of black raspberry and strawberry extracts on BaPDE-induced activation of transcription factors and their target genes

Mol Carcinog. 2008 Apr;47(4):286-94. doi: 10.1002/mc.20377.


The chemopreventive properties of edible berries have been demonstrated both in vitro and in vivo, however, the specific molecular mechanisms underlying their anti-cancer effects are largely unknown. Our previous studies have shown that a methanol extract fraction of freeze-dried black raspberries inhibits benzoapyrene (BaP)-induced transformation of Syrian hamster embryo cells. This fraction also blocks activation of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) induced by benzoapyrene diol-epoxide (BaPDE) in mouse epidermal JB6 Cl 41 cells. To determine if different berry types exhibit specific mechanisms for their anti-cancer effects, we compared the effects of extract fractions from both black raspberries and strawberries on BaPDE-induced activation of various signaling pathways in Cl 41 cells. Black raspberry fractions inhibited the activation of AP-1, NF-kappaB, and nuclear factor of activated T cells (NFAT) by BaPDE as well as their upstream PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. In contrast, strawberry fractions inhibited NFAT activation, but did not inhibit the activation of AP-1, NF-kappaB or the PI-3K/Akt-p70(S6K) and mitogen-activated protein kinase pathways. Consistent with the effects on NFAT activation, tumor necrosis factor-alpha (TNF-alpha) induction by BaPDE was blocked by extract fractions of both black raspberries and strawberries, whereas vascular endothelial growth factor (VEGF) expression, which depends on AP-1 activation, was suppressed by black raspberry fractions but not strawberry fractions. These results suggest that black raspberry and strawberry components may target different signaling pathways in exerting their anti-carcinogenic effects.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / pharmacology*
  • Animals
  • Anticarcinogenic Agents / chemistry
  • Carcinogens / pharmacology
  • Cell Line
  • Cricetinae
  • Fragaria* / chemistry
  • Fragaria* / physiology
  • Fruit / chemistry
  • Fruit / physiology
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Mice
  • NF-kappa B / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Transcription Factor AP-1 / antagonists & inhibitors
  • Transcription Factor AP-1 / metabolism*
  • Transcription Factors / metabolism*


  • Anticarcinogenic Agents
  • Carcinogens
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor AP-1
  • Transcription Factors
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide