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Trends Food Sci Technol. 2017 Nov;69(Pt B):257-269. doi: 10.1016/j.tifs.2017.02.002. Epub 2017 Feb 16.

KEAP1 and Done? Targeting the NRF2 Pathway with Sulforaphane.

Author information

1
Jacqui Wood Cancer Centre, Division of Cancer Research, School of Medicine, University of Dundee, Dundee, DD1 9SY, Scotland, UK.
2
Lewis B. and Dorothy Cullman Chemoprotection Center, Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
3
Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4
Center for Human Nutrition, Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
5
Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15261 USA.

Abstract

Background:

Since the re-discovery of sulforaphane in 1992 and the recognition of the bioactivity of this phytochemical, many studies have examined its mode of action in cells, animals and humans. Broccoli, especially as young sprouts, is a rich source of sulforaphane and broccoli-based preparations are now used in clinical studies probing efficacy in health preservation and disease mitigation. Many putative cellular targets are affected by sulforaphane although only one, KEAP1-NRF2 signaling, can be considered a validated target at this time. The transcription factor NRF2 is a master regulator of cell survival responses to endogenous and exogenous stressors.

Scope and Approach:

This review summarizes the chemical biology of sulforaphane as an inducer of NRF2 signaling and efficacy as an inhibitor of carcinogenesis. It also provides a summary of the current findings from clinical trials using a suite of broccoli sprout preparations on a series of short-term endpoints reflecting a diversity of molecular actions.

Key Findings and Conclusions:

Sulforaphane, as a pure chemical, protects against chemical-induced skin, oral, stomach, colon, lung and bladder carcinogenesis and in genetic models of colon and prostate carcinogenesis. In many of these settings the antitumorigenic efficacy of sulforaphane is dampened in Nrf2-disrupted animals. Broccoli preparations rich in glucoraphanin or sulforaphane exert demonstrable pharmacodynamic action in over a score of clinical trials. Measures of NRF2 pathway response and function are serving as guideposts for the optimization of dose, schedule and formulation as clinical trials with broccoli-based preparations become more commonplace and more rigorous in design and implementation.

KEYWORDS:

KEAP1; NRF2; clinical trial; cytoprotection; sulforaphane

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