title: The molecular basis that unifies the metabolism, cellular uptake and chemopreventive activities of dietary isothiocyanates.
abstract: Organic isothiocyanates (ITCs), which are characterized by the presence of an -N=C=S group, are among the most extensively studied cancer chemopreventive agents and show highly promising chemopreventive activities. Numerous studies have shown that ITCs can inhibit both carcinogenesis and cancer growth in a variety of animal models. Many cruciferous vegetables, which are commonly consumed by humans, are rich sources of these compounds. Of particular interest are their high bioavailability, their shared metabolic profile and their ability to target a wide array of cancer-related cellular proteins. This review is focused on discussing the molecular basis of these intriguing properties of ITCs, with a particular emphasis on the concept that cellular uptake and metabolism of ITCs and at least some of their major chemopreventive activities are all initiated through direct reaction of the carbon atom of the -N=C=S group of the ITCs with cysteine sulfhydryl groups of glutathione (GSH) and of proteins. This knowledge deepens our understanding about the biological activities of ITCs and may facilitate further research and development of these compounds for cancer prevention and treatment.
authors.affiliation: Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263, USA. yuesheng.zhang@roswellpark.org
authors.forename: Yuesheng
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism*; D004032:Diet; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D047908:Intracellular Signaling Peptides and Proteins; D017879:Isothiocyanates; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; D051197:Toll-Like Receptor 4; D018808:Transcription Factor AP-1; D014404:Tubulin
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