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Nrf2: control of sensitivity to carcinogens
Stephen L Slocum1, Thomas W Kensler
1Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Archives of Toxicology
|March 4, 2011
Summary
Chemoprevention strategies using enzyme inducers show promise for cancer prevention. The Nrf2 (NF-E2-related factor 2) pathway is crucial for detoxifying carcinogens and protecting against DNA damage, highlighting its role in cancer susceptibility.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Enzyme induction is a key chemoprevention strategy against chemical carcinogens.
- Agents like phenolic antioxidants and dithiolethiones are in clinical trials for cancer prevention.
- The NF-E2-related factor 2 (Nrf2) pathway regulates detoxifying enzymes.
Purpose of the Study:
- To define the molecular basis of chemoprevention by enzyme-inducing agents.
- To elucidate the role of the Nrf2 pathway in cytoprotection and cancer prevention.
- To understand Nrf2's regulation of cellular defense mechanisms against carcinogens.
Main Methods:
- Review of pre-clinical and clinical studies on chemoprevention agents.
- Identification and characterization of the Nrf2 transcription factor.
- Analysis of Nrf2-disrupted mouse models in various cancer models.
Main Results:
- Nrf2 regulates a broad cytoprotective transcriptional response.
- Nrf2 activation leads to enhanced detoxification of reactive electrophiles and oxidants.
- Nrf2-disrupted mice show increased susceptibility to various cancers.
Conclusions:
- The Nrf2 pathway is a critical determinant of susceptibility to carcinogenesis.
- Targeting the Nrf2 pathway holds potential for cancer chemoprevention.
- Understanding Nrf2's role is vital for developing effective cancer prevention strategies.
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