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Chemoprotection Against Cancer by Isothiocyanates: A Focus on the Animal Models and the Protective Mechanisms

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Natural Products in Cancer Prevention and Therapy

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 329))

Abstract

The isothiocyanates are among the most extensively studied chemoprotective agents. They are derived from glucosinolate precursors by the action of β-thioglucosidase enzymes (myrosinases). The Cruciferae family represents a rich source of glucosinolates. Notably, nearly all of the biological activities of glucosinolates, in both plants and animals, are attributable to their cognate hydrolytic products, and the isothiocyanates are prominent examples. In contrast to their relatively inert glucosinolate precursors, the isothiocyanates are endowed with high chemical reactivity, especially with sulfur-centered nucleophiles, such as protein cysteine residues. There are numerous examples of the chemoprotective effects of isothiocyanates in a number of animal models of experimental carcinogenesis at various organ sites and against carcinogens of several different types. It is becoming increasingly clear that this efficient protection is due to multiple mechanisms, including induction of cytoprotective proteins through the Keap1/Nrf2/ARE pathway, inhibition of proinflammatory responses through the NFκB pathway, induction of cell cycle arrest and apoptosis, effects on heat shock proteins, and inhibition of angiogenesis and metastasis. Because the isothiocyanates affect the function of transcription factors and ultimately the expression of networks of genes, such protection is comprehensive and long-lasting.

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Acknowledgments

The author is very grateful to Research Councils UK and Cancer Research UK (C20953/A10270) for financial support.

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Authors and Affiliations

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

    Albena T. Dinkova-Kostova

  2. Departments of Medicine and Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA

    Albena T. Dinkova-Kostova

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  1. Albena T. Dinkova-Kostova
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Correspondence to Albena T. Dinkova-Kostova .

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  1. College of Pharmacy, University of Hawaii, Rainbow Drive 34, Hilo, 96720, Hawaii, USA

    John M. Pezzuto

  2. Ernest Mario School of Pharmacy, Department of Chemical Biology, Rutgers University, Frelinghuysen Road 164, Piscataway, 08854-0789, New Jersey, USA

    Nanjoo Suh

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Dinkova-Kostova, A.T. (2012). Chemoprotection Against Cancer by Isothiocyanates: A Focus on the Animal Models and the Protective Mechanisms. In: Pezzuto, J., Suh, N. (eds) Natural Products in Cancer Prevention and Therapy. Topics in Current Chemistry, vol 329. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2012_337

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