Nutrition and the Risk of Common Forms of Cancer
David Heber, Zhaoping Li in Primary Care Nutrition, 2017
Dietary glucosinolates are hydrolyzed by a plant enzyme called myrosinase when the vegetable is crushed, releasing the volatile metabolites, such as isothiocyanate. These compounds travel to the liver and induce phase 2 detoxifying enzymes, including glutathione S-transferases and UDP glucuronosyl transferases (UGTs). These enzymes in the liver catalyze conjugation reactions to inactivate or detoxify exogenous carcinogens and endogenous compounds, including sex steroid hormones related to cancer development (Mansuy 2011; Navarro et al. 2011; Boddupalli et al. 2012). Indole glucosinolate hydrolysis products, such as di-indolyl methane and indole-3-carbinol, also induce both phase 1 drug metabolic and phase 2 detoxifying enzymes by direct interaction with aryl-hydrocarbon receptor (AhR) or increasing the binding affinity of AhR to xenobiotic response elements (XREs) in target genes (Navarro et al. 2011).
From Designer Food Formulation to Oxidative Stress Mitigation: Health-Boosting Constituents of Cabbage
Megh R. Goyal, Hafiz Ansar Rasul Suleria, Ramasamy Harikrishnan in The Role of Phytoconstitutents in Health Care, 2020
Numerous studies have depicted that cruciferous vegetables possess a complex combination of bioactive ingredients, minerals, and antioxidant vitamins that could scavenge ROS, ultimately improving the levels of GSH, SOD, and CAT. Besides other ingredients, the GLS-myrosinase system exists inherently in brassica vegetables, and myrosinase hydro-lyzes GLS to isothiocyanates. The myrosinase is either natively present within the compartments of plant cells or in the mammalian intestine. It is still unclear that these S-containing compounds are either responsible for lowering cholesterol levels or the synergistic effect of several antioxidants in cabbage to improve the overall antioxidant status. Recent investigation on broccoli has associated isothiocyanates and sulforaphane with cholesterol-lowering activity [96].
Nutraceuticals’ Role in Proliferation and Prevention of Breast Cancer
Sheeba Varghese Gupta, Yashwant V. Pathak in Advances in Nutraceutical Applications in Cancer, 2019
High intake of fruits and vegetables has shown a possible benefit in the reduction of breast cancer risk. Cruciferous vegetables such a broccoli, cabbage, cauliflower, and Brussel sprouts contain high content of glucosinolates, and when eaten as raw vegetables, or chewed, an enzyme called myrosinase is released that converts glucosinolates into isothiocyanates [22]. This compound is known for its chemoprotective activity in cancer including breast cancer. The isothiocyanates are of different types and act in different ways; for example, benzyl isothiocyanate induced inhibition is associated with apoptotic cell death. The underlying mechanism of isothiocyanates seems to be mainly through the downregulation of ER and their signaling as well as apoptosis and cell cycle arrest, thus preventing the spread of cancer cells.
Bioactivation of herbal constituents: mechanisms and toxicological relevance
Published in Drug Metabolism Reviews, 2019
Bo Wen, Peter Gorycki
Although ITCs are electrophiles capable of covalently modifying proteins, they occur in plants as glucosinolates (β-thioglucoside-N-hydrosulfates, Figure 16). When the physical structure of the vegetable is damaged, for example cutting or chewing, the enzyme myrosinase (β-thioglucoside glucohydrolase) present in cruciferous vegetables comes into contact with the glucosinolate converting it to an unstable thiohydroximate O-sulfonate, which yields the electrophilic isothiocyanate via Lossen rearrangement (Figure 16). Conjugation with glutathione (GSH) is the principal metabolic pathway of ITCs which readily react with the cysteine residue in GSH through thiocarbamation, a covalent bond formation between the electrophilic carbon atom in the ITC moiety and the sulfhydryl group in GSH. Reaction of the –N=C=S group with intracellular GSH drives rapid ITC accumulation in cells as the conjugates are unstable and readily dissociate to their parent compounds. GSH conjugation of ITCs is also facilitated by human GSTs, in particular GSTs M1-1 and P1-1 (Kolm et al. 1995). The formed dithiocarbamates are typically excreted as mercapturic acids in both urine and bile. The electrophilic carbon of ITCs also reacts irreversibly with amine groups in proteins to form stable thioureas with much slower rates of reaction (Brown et al. 2009). In addition, ITCs can undergo CYP-mediated oxidative desulfuration to electrophilic isocyanates leading to the formation of S-thiocarbamate conjugates (Figure 16) (Lee 1996; Yoshigae et al. 2013).
Nanoencapsulation of sulforaphane in broccoli membrane vesicles and their in vitro antiproliferative activity
Published in Pharmaceutical Biology, 2021
Lucía Yepes-Molina, Micaela Carvajal
Characterizations to determine the content of isothiocyanates that may remain in the BM-vesicles after the isolation process was carried out. BM-vesicles were isolated from broccoli leaves, which also contain a considerable amount of GLSs (precursors of ITCs) (Liu et al. 2018). GLSs were not detected when BM-vesicles were analyzed by UHPLC-QqQ-MS/MS, although different ITCs were detected (SFN, erucin, iberine, and indole-3-carbinol). The transformation of GLSs to ITCs may be due, on the one hand, to the isolation process of the vesicles, which involves aggressive procedures, such as trituration or ultracentrifugation involving the myrosinase enzyme, responsible for the conversion (Martinez-Ballesta and Carvajal 2015). Myrosinase is usually found as myrosinase grains inside of the vacuole, but there are also indications that it may appear associated with the tonoplast (Lüthy and Matile 1984; Chhajed et al. 2019) and therefore it is possible that BM-vesicles contained some associated myrosinase. In fact, myrosinase was detected in the BM-vesicles proteomic analysis, and its activity in BM-vesicles was measured using sinigrin as the substrate (data not shown). Thus, BM-vesicles act as a nanocarrier, but may also contain some ITCs compounds that could affect the treatment of melanocytes in addition to SFN. In fact, all of the ITCs identified in the BM-vesicles have been previously studied due to their health benefits to human health, as they show antimicrobial, antiviral, antioxidant, and anticancer activities (Mitsiogianni et al. 2019; Singh et al. 2021).
The Potential for Reducing Lynch Syndrome Cancer Risk with Nutritional Nrf2 Activators
Published in Nutrition and Cancer, 2021
Andrew Aussem, Kirsten Ludwig
Sulforaphane is a phytochemical of the organosulfur compound classification known as an isothiocyanate and found predominantly in the cruciferous vegetable family, particularly Brassica oleracea (76, 82, 87). Common culinary vegetables in the Brassica oleracea family include broccoli, cabbage, cauliflower, kale, Brussels sprouts, collard greens, savoy, and kohlrabi. However, sulforaphane itself is not present in these vegetables, its precursor glucoraphanin (GRN) and a vacuole enzyme Myrosinase (MYR) are present (76, 82). MYR is found within the cells of Brassica vegetables, separately compartmentalized from GRN, and when the cell wall is ruptured (ex. chewing, cutting, and/or crushing), MYG and GRN interact to produce sulforaphane (76, 82). As with the other mentioned phytochemicals, sulforaphane and cruciferous vegetable intake have been linked to multiple health benefits including reducing the risk of many chronic diseases such as cancer, diabetes, obesity, cardiovascular disease, and neurodegeneration (82, 87, 132–137). Sulforaphane is not a direct free radical scavenger and the health benefits of this compound are mainly hypothesized to be due to its potent ability to activate the Nrf2 pathway (76, 82, 87). Sulforaphane has been shown to activate the Nrf2 pathway through two mechanisms. Sulforaphane is able to alter Keap1 in a cysteine dependant manner and has also been shown to activate upstream kinases leading to Nrf2 phosphorylation; both scenarios triggering Nrf2 translocation to the nucleus (76, 82, 87).
Related Knowledge Centers
- Catalysis
- Chemical Reaction
- Enzyme
- Glucose
- Hydrolysis
- Plant Defense Against Herbivory
- Protein Data Bank
- Glycoside Hydrolase
- Glucosinolate
- Substrate