glucoraphanin and Neoplasms

Sulforaphane is an isothiocyanate occurring in stored form as glucoraphanin in cruciferous vegetables such as cabbage, cauliflower, and kale, and at high levels in broccoli especially in broccoli sprouts. Glucoraphanin requires the plant enzyme myrosinase for converting it into sulforaphane. Sulforaphane is metabolized through mercapturic acid pathway, being conjugated with glutathione and undergoes further biotransformation, yielding metabolites. Sulforaphane is extensively investigated and is in the interest in medicine for its health benefits. It has been shown that sulforaphane may protect against various types of cancer, may also decrease the risk of cardiovascular disease, and help in autism and osteoporosis. Our review offers a short summary of interesting properties of sulforaphane. Both the in vitro and in vivo methods/models and clinical studies are mentioned.

Topics: Animals; Antineoplastic Agents, Phytogenic; Autistic Disorder; Brassica; Glucosinolates; Humans; Imidoesters; Isothiocyanates; Neoplasms; Osteoporosis; Oximes; Sulfoxides

With the properties of efficacy, safety, tolerability, practicability and low cost, foods containing bioactive phytochemicals are gaining significant attention as elements of chemoprevention strategies against cancer. Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate produced by cruciferous vegetables such as broccoli, is found to be a highly promising chemoprevention agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach or bladder, but also cardiovascular disease, neurodegenerative diseases, and diabetes. For reasons of experimental exigency, preclinical studies have focused principally on sulforaphane itself, while clinical studies have relied on broccoli sprout preparations rich in either sulforaphane or its biogenic precursor, glucoraphanin. Substantive subsequent evaluation of sulforaphane pharmacokinetics and pharmacodynamics has been undertaken using either pure compound or food matrices. Sulforaphane affects multiple targets in cells. One key molecular mechanism of action for sulforaphane entails activation of the Nrf2-Keap1 signaling pathway although other actions contribute to the broad spectrum of efficacy in different animal models. This review summarizes the current status of pre-clinical chemoprevention studies with sulforaphane and highlights the progress and challenges for the application of foods rich in sulforaphane and/or glucoraphanin in the arena of clinical chemoprevention.

Topics: Animals; Anticarcinogenic Agents; Brassica; Chemoprevention; Glucosinolates; Humans; Imidoesters; Isothiocyanates; Neoplasms; NF-E2-Related Factor 2; Oximes; Signal Transduction; Sulfoxides; Vegetables

Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin (GRA), which is found in great amounts especially in broccoli. Its consumption has been reported to be associated with a lower risk of myocardial infarction and cancer development. Additionally, its effects have been studied in neurodegenerative diseases, diabetes, and atherosclerosis, most of the times using animal models and cell cultures.. Given the promising results of SFN, this review aimed to investigate evidence documented in human intervention studies with broccoli, GRA and SFN.. A search was performed on PubMed and Virtual Health Library databases by two independent researchers using the descriptors "broccoli" or "glucoraphanin" or "sulforaphane", which should appear on the study's title or abstract. This review included randomized clinical trials performed in humans that were published in English and Portuguese from 2003 to 2013 and that considered clinical and molecular parameters of cell damage as outcomes of interest.. Seventeen studies were selected, and the predominant type of intervention was broccoli sprouts. More consistent results were obtained for the clinical parameters blood glucose and lipid profile and for molecular parameters of oxidative stress, indicating that there was an improvement in these parameters after intervention. Less solid evidence was found with regard to decreased inflammation, Helicobacter pylori colonization, and protection against cancer.. Although being relevant, the evidence for the use of broccoli, GRA and SFN in humans are limited; thus, further intervention studies are needed to evaluate outcomes more consistently and reach better grounded conclusions.. Introducción: El sulforafano (SFN) es un isotiocianato derivado de la glucorafanina (GRA), encontrada en gran cantidad especialmente en el brócolis. Su consumo está asociado a un menor riesgo de infarto del miocardio y de cáncer. Además, sus efectos están siendo estudiados en enfermedades neurodegenerativas, diabetes y aterosclerosis, casi siempre utilizando modelos animales y cultivos celulares. Objetivos: Debido a los resultados prometedores del compuesto SFN, esta revisión buscó investigar evidencias ya documentadas en intervenciones con brócoli, GRA y SFN en humanos. Métodos: Se realizó una búsqueda en las bases de datos PubMed y Biblioteca Virtual en Salud, por dos investigadores independientes, utilizando los descriptores “broccoli” o “glucoraphanin” o “sulforaphane”, que debían constar en el título o resumen del trabajo. Se incluyeron ensayos clínicos randomizados realizados en humanos, publicados en inglés y portugués entre 2003 y 2013, y que consideraron como desenlaces de interés parámetros clínicos y moleculares de daño celular. Resultados: Se seleccionaron 17 estudios y el tipo de intervención predominante fueron brotes de brócoli. Los resultados más consistentes fueron obtenidos con los parámetros clínicos glicemia y perfil lipídico y los parámetros moleculares de estrés oxidativo, que presentaron mejora después de la intervención. Se encontraron evidencias menos sólidas respeto a la disminución de la inflamación, de la colonización por Helicobacter pylori y protección contra cáncer. Conclusión: Aunque relevantes, las evidencias del uso de brócoli, GRA y SFN en humanos son limitadas, siendo necesarios más estudios de intervención para avaluar los desenlaces de forma más consistente y producir conclusiones mejor fundamentadas.

Topics: Anticarcinogenic Agents; Brassica; Diet; Glucosinolates; Humans; Imidoesters; Isothiocyanates; Myocardial Infarction; Neoplasms; Oximes; Sulfoxides

Topics: Animals; Aniridia; Anticarcinogenic Agents; Antioxidants; Brassica; Cardiovascular Diseases; Cerebellar Ataxia; Clinical Trials as Topic; Glucosinolates; Humans; Imidoesters; Intellectual Disability; Neoplasms; Oxidative Stress; Oximes; Sulfoxides

Sulforaphane (SF) is a chemopreventive isothiocyanate (ITC) derived from glucoraphanin (GRP) hydrolysis by myrosinase, a thioglucoside present in broccoli. The ability of broccoli powders sold as supplements to provide dietary SF is often of concern as many supplements contain GRP, but lack myrosinase. In a previous study, biomarkers of SF bioavailability from a powder rich in GRP, but lacking myrosinase, were enhanced by co-consumption of a myrosinase-containing air-dried broccoli sprout powder. Here, we studied the absorption of SF from the GRP-rich powder used in the previous study, but in combination with fresh broccoli sprouts, which are commercially available and more applicable to the human diet than air-dried sprout powder. A total of four participants each consumed four meals (separated by 1 week) consisting of dry cereal and yogurt with sprouts equivalent to 70 μmol SF, GRP powder equivalent to 120 μmol SF, both or neither. Metabolites of SF were analysed in blood and urine. The 24 h urinary SF-N-acetylcysteine recovery was 65, 60 and 24 % of the dose ingested from combination, broccoli sprout and GRP powder meals, respectively. In urine and plasma, ITC appearance was delayed following the GRP powder meal compared with the sprout and combination meals. Compared with the GRP powder or sprouts alone, combining broccoli sprouts with the GRP powder synergistically enhanced the early appearance of SF, offering insight into the combination of foods for improved health benefits of foods that reduce the risk for cancer.

Topics: Absorption; Acetylcysteine; Adolescent; Adult; Anticarcinogenic Agents; Biomarkers; Brassica; Cross-Over Studies; Diet; Dietary Supplements; Glucosinolates; Humans; Hydrolysis; Imidoesters; Isothiocyanates; Male; Neoplasms; Nutritional Sciences; Oximes; Powders; Sulfoxides; Surveys and Questionnaires; Young Adult

As a cytosolic transcription factor, the aryl hydrocarbon (Ah) receptor is involved in several patho- physiological events leading to immunosuppression and cancer; hence antagonists of the Ah receptor may possess chemoprevention properties. It is known to modulate carcinogen-metabolising enzymes, for instance the CYP1 family of cytochromes P450 and quinone reductase, both important in the biotransformation of many chemical carcinogens via regulating phase I and phase II enzyme systems. Utilising chemically-activated luciferase expression (CALUX) assay it was revealed that intact glucosinolates, glucoraphanin and glucoerucin, isolated from Brassica oleracea L. var. acephala sabellica and Eruca sativa ripe seeds, respectively, are such antagonists. Both glucosinolates were poor ligands for the Ah receptor; however, they effectively antagonised activation of the receptor by the avid ligand benzo[a]pyrene. Indeed, intact glucosinolate glucoraphanin was a more potent antagonist to the receptor than glucoerucin. It can be concluded that both glucosinolates effectively act as antagonists for the Ah receptor, and this may contribute to their established chemoprevention potency.

Topics: Brassicaceae; Glucose; Glucosinolates; Humans; Imidoesters; Neoplasms; Oximes; Receptors, Aryl Hydrocarbon; Sulfoxides

Epidemiological studies have demonstrated reduced risk of developing cancer upon consumption of diets rich in cruciferous vegetables. This chemoprevention has been largely attributed to the presence of the natural products glucosinolates, particularly the methionine-derived glucoraphanin from broccoli. Improved nutrition by functional foods or health-promoting dietary supplements is an attractive means for prevention of lifestyle-based diseases. Towards this goal, we have engineered the glucoraphanin pathway into tobacco. First, we engineered elongation of the side chain of methionine to produce the key intermediate dihomo-methionine. This process is catalyzed through two cycles in a chain-elongation pathway that takes place partly in the cytosol and partly in the chloroplast. Second, by coupling the five enzymes of the chain-elongation pathway to eight enzymes of the glucosinolate pathway, we show production of glucoraphanin together with other glucosinolates derived from chain-elongated isoleucine and/or leucine. The conversion of methionine to glucoraphanin is obtained via 14 intermediates. Demonstrating the production of the high-value glucoraphanin in a heterologous host has great potential in the food and medicinal industry as a means to generate a stable, rich source of glucoraphanin for the benefit of human health.

Topics: Glucosinolates; Imidoesters; Neoplasms; Nicotiana; Oximes; Sulfoxides