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Nrf2: a potential molecular target for cancer chemoprevention by natural compounds

Woo-Sik Jeong1, Mira Jun, Ah-Ng Tony Kong

  • 1Food Science Institute, School of Food & Life Science, College of Biomedical Science & Engineering, Inje University, South Korea.

Antioxidants & Redox Signaling
|February 21, 2006
PubMed

Insights

Cancer chemoprevention involves protecting cells from carcinogens by inducing detoxifying enzymes via the Nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. This pathway is a key molecular target for developing new cancer preventive agents.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer chemoprevention aims to protect against carcinogens by enhancing cellular defense mechanisms.
  • Phase 2 detoxifying and antioxidant enzymes, like glutathione S-transferase, are crucial for this protection.
  • The antioxidant response element (ARE) pathway, primarily regulated by Nuclear factor-erythroid 2-related factor 2 (Nrf2), controls the expression of these protective enzymes.

Purpose of the Study:

  • To review the Nrf2/ARE pathway's role in cancer chemoprevention.
  • To explore the potential of natural compounds in activating this pathway.
  • To assess the feasibility of using Nrf2/ARE activators as human cancer preventive agents.

Main Methods:

  • The review synthesizes current understanding of the Nrf2/ARE pathway's molecular mechanisms.
  • It discusses upstream signaling pathways regulating Nrf2 activity, including MAPK and PI3K.
  • The role of natural chemopreventive agents in modulating Nrf2 protein turnover and ARE-dependent gene expression is examined.

Main Results:

  • Nrf2, sequestered by Keap1 under normal conditions, translocates to the nucleus upon induction, activating protective genes.
  • Various signaling pathways and natural compounds influence Nrf2/ARE activity.
  • Natural compounds can induce Nrf2/ARE-dependent gene expression, offering a strategy for cancer prevention.

Conclusions:

  • The Nrf2/ARE pathway is a promising molecular target for cancer chemoprevention.
  • Screening natural compounds for Nrf2/ARE pathway activation is feasible.
  • Targeting the Nrf2/ARE pathway holds potential for developing novel cancer preventive agents for human use.

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