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Resveratrol inhibits phorbol ester and UV-induced activator protein 1 activation by interfering with

R Yu1, V Hebbar, D W Kim

  • 1Department of Pharmaceutics and Pharmacodynamics, Center for Pharmaceutical Biotechnology, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois, USA.

Molecular Pharmacology
|June 16, 2001
PubMed

Insights

Resveratrol inhibits cancer-promoting activator protein 1 (AP-1) and mitogen-activated protein kinase (MAPK) pathways. This chemopreventive effect may stem from resveratrol

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • Resveratrol, a natural phenolic compound, exhibits chemopreventive properties against chemical-induced carcinogenesis in animal models.
  • Activator protein 1 (AP-1) is a critical transcription factor implicated in carcinogenesis and tumor transformation.
  • Understanding resveratrol's mechanism against cancer requires investigating its effects on key signaling pathways like AP-1.

Purpose of the Study:

  • To elucidate the chemopreventive mechanism of resveratrol by examining its effects on Activator protein 1 (AP-1) activity.
  • To investigate resveratrol's impact on mitogen-activated protein kinase (MAPK) pathways, which are crucial for AP-1 activation.
  • To identify the specific molecular targets of resveratrol within the AP-1 and MAPK signaling cascades.

Main Methods:

  • HeLa cells were pretreated with resveratrol and then stimulated with ultraviolet C (UVC) or phorbol 12-myristate 13-acetate (PMA).
  • AP-1 reporter gene transcription and the activation of ERK2, JNK1, and p38 kinases were measured.
  • The study utilized dominant-negative mutants of kinases, isolated protein kinases, and selective kinase inhibitors to probe signaling pathways.

Main Results:

  • Resveratrol pretreatment significantly inhibited UVC- and PMA-induced AP-1 reporter gene transcription.
  • Resveratrol suppressed the activation of extracellular signal-regulated protein kinase 2 (ERK2), c-jun N-terminal kinase 1 (JNK1), and p38.
  • Resveratrol diminished the kinase activities of c-Src protein tyrosine kinase and protein kinase C, suggesting these as potential targets.

Conclusions:

  • Resveratrol exerts chemopreventive effects by inhibiting AP-1 and MAPK signaling pathways.
  • The mechanism involves the suppression of protein tyrosine kinases and protein kinase C activities.
  • These findings provide molecular insights into how resveratrol may prevent cancer development.

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