Cancer-preventive isothiocyanates: measurement of human exposure and mechanism of action.
Numerous studies in rodents have documented the cancer-preventive activity of a significant number of isothiocyanates (ITCs), the majority of which occur in plants, especially in cruciferous vegetables. Dietary ITCs may play an important role in the prevention of human cancers. Several recent epidemiological studies have already shown that dietary consumption of ITCs inversely correlates with the risk of developing lung, breast and colon cancers. ITCs are principally metabolized through the mercapturic acid pathway in vivo, giving rise to N-acetylcysteine conjugates, which are excreted in the urine. Analytical methods have been developed to allow detection of ITCs and their metabolites formed in the mercapturic acid pathway. Studies show that total urinary level of ITC equivalent is an excellent biomarker of human exposure to ITCs. Moreover, these methods also have made it possible to learn the bioavailability of ITCs from cruciferous vegetables. ITCs possess multiple anticarcinogenic mechanisms, including inhibition of carcinogen-activating enzymes, induction of carcinogen-detoxifying enzymes, increase of apoptosis, arrest of cell cycle progression, as well as several other mechanisms that are not yet fully described. These mechanisms, which are discussed in detail in this review, illustrate the remarkable ability of ITCs to inhibit cancer development-effective against both developing and developed cancer cells.
Department of Chemoprevention, Roswell Park Cancer Institute, Basic Science 711, Elm and Carlton Streets, Buffalo, NY 14263, USA. yuesheng.zhang@roswellpark.org
Yuesheng
Y
Zhang
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects*; D018890:Chemoprevention; D065607:Cytochrome P-450 Enzyme Inhibitors; D004032:Diet; D006801:Humans; D017879:Isothiocyanates / Q000627:therapeutic use*; D009369:Neoplasms / Q000201:enzymology / Q000517:prevention & control*; D011379:Prognosis; D014675:Vegetables
D016588:Anticarcinogenic Agents; D015415:Biomarkers; D065607:Cytochrome P-450 Enzyme Inhibitors; D017879:Isothiocyanates