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Sulfhydryl-Reactive Phytochemicals as Dual Activators of Transcription Factors NRF2 and HSF1

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50 Years of Phytochemistry Research

Part of the book series: Recent Advances in Phytochemistry ((RAPT,volume 43))

Abstract

Two central regulators, nuclear factor-erythroid 2 p45-related factor 2 (NRF2) and heat shock factor 1 (HSF1), control the KEAP1/NRF2/ARE pathway and the heat shock response, two essential cellular defense mechanisms. Both systems are highly inducible under conditions of stress. Many small molecules, including certain phytochemicals, such as isothiocyanates and phenylpropanoids, and/or their metabolites, have the capacity to induce the KEAP1/NRF2/ARE pathway. Recent results suggest that a common signal that is sensed through cysteine modification(s) within Kelch-like ECH-associated protein 1 (KEAP1) and HSF1, or possibly within a negative regulator of HSF1, is responsible for triggering both pathways. Celastrol, withaferin A, gedunin, curcumin, and sulforaphane are examples of structurally diverse phytochemicals with a common chemical signature: reactivity with sulfhydryl groups. This reactivity underlies their biological activities as multitarget agents for which protective effects have been documented in numerous animal models of human disease and which include induction of large networks of transcriptional programs regulated by transcription factors NRF2 and HSF1.

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Acknowledgments

The authors are extremely grateful to the Biotechnology and Biological Sciences Research Council (BBSRC, Project Grant BB/J007498/1) and Research Councils UK for financial support.

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Authors and Affiliations

  1. Division of Cancer Research, Medical Research Institute, University of Dundee, DD1 9SY, Dundee, Scotland, UK

    Albena T. Dinkova-Kostova, Ying Zhang, Sharadha Dayalan Naidu, Rumen V. Kostov & Ashley Pheely

  2. Department of Chemistry, University of Catania, 95100, Catania, Italy

    Vittorio Calabrese

  3. Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Albena T. Dinkova-Kostova

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  1. Albena T. Dinkova-Kostova
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  2. Ying Zhang
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  3. Sharadha Dayalan Naidu
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  4. Rumen V. Kostov
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  6. Vittorio Calabrese
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Correspondence to Albena T. Dinkova-Kostova .

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  1. Institute of Biological Chemistry, Washington State University, Pullman, Washington, USA

    David R. Gang

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Dinkova-Kostova, A., Zhang, Y., Naidu, S., Kostov, R., Pheely, A., Calabrese, V. (2013). Sulfhydryl-Reactive Phytochemicals as Dual Activators of Transcription Factors NRF2 and HSF1. In: Gang, D. (eds) 50 Years of Phytochemistry Research. Recent Advances in Phytochemistry, vol 43. Springer, Cham. https://doi.org/10.1007/978-3-319-00581-2_6

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