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A strategy for cancer prevention: stimulation of the Nrf2-ARE signaling pathway

Yuesheng Zhang1, Gary B Gordon

  • 1Department of Chemoprevention, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. yuesheng.zhang@roswellpark.org

Molecular Cancer Therapeutics
|July 15, 2004
PubMed

Insights

Chemicals that activate the antioxidant response element (ARE) pathway can prevent cancer. This pathway involves nuclear factor erythroid 2-related factor 2 (Nrf2) and protects cells from toxins.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cancer Research

Background:

  • Many genes protecting cells from carcinogens and toxins are regulated by the antioxidant response element (ARE).
  • Increased expression of ARE-regulated genes is linked to cancer inhibition.
  • The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in ARE activation.

Purpose of the Study:

  • To elucidate the signaling pathway leading to ARE activation.
  • To identify chemical agents that stimulate the ARE pathway for cancer prevention.

Main Methods:

  • Investigated the role of Nrf2 in ARE-mediated gene regulation.
  • Identified chemical agents (ARE-mediated inducers) that activate the Nrf2-ARE pathway.
  • Developed assays to detect ARE-mediated inducers.

Main Results:

  • Nrf2 is sequestered by Kelch-like ECH-associated protein 1 in the cytoplasm.
  • ARE-mediated inducers cause Nrf2 to translocate to the nucleus and bind to ARE.
  • Several identified ARE-mediated inducers show promising cancer preventive activity.

Conclusions:

  • The Nrf2-ARE signaling pathway is crucial for cellular defense against toxins and cancer.
  • Targeting the Nrf2-ARE pathway with specific inducers represents a potential strategy for cancer prevention.

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