The consumption of cruciferous vegetables has long been associated with a reduced risk in the occurrence of cancer at various sites, including the prostate, lung, breast and colon. This protective effect is attributed to isothiocyanates present in these vegetables, and sulforaphane (SF), present in broccoli, is by far the most extensively studied to uncover the mechanisms behind this chemoprotection. The major mechanism by which SF protects cells was traditionally thought to be through Nrf2-mediated induction of phase 2 detoxification enzymes that elevate cell defense against oxidative damage and promote the removal of carcinogens. However, it is becoming clear that there are multiple mechanisms activated in response to SF, including suppression of cytochrome P450 enzymes, induction of apoptotic pathways, suppression of cell cycle progression, inhibition of angiogenesis and anti-inflammatory activity. Moreover, these mechanisms seem to have some degree of interaction to synergistically afford chemoprevention.
Glucosinolates (GLSs) are found in Brassica vegetables. Examples of these sources include cabbage, Brussels sprouts, broccoli, cauliflower and various root vegetables (e.g. radish and turnip). A number of epidemiological studies have identified an inverse association between consumption of these vegetables and the risk of colon and rectal cancer. Animal studies have shown changes in enzyme activities and DNA damage resulting from consumption of Brassica vegetables or isothiocyanates, the breakdown products (BDP) of GLSs in the body. Mechanistic studies have begun to identify the ways in which the compounds may exert their protective action but the relevance of these studies to protective effects in the human alimentary tract is as yet unproven. In vitro studies with a number of specific isothiocyanates have suggested mechanisms that might be the basis of their chemoprotective effects. The concentration and composition of the GLSs in different plants, but also within a plant (e.g. in the seeds, roots or leaves), can vary greatly and also changes during plant development. Furthermore, the effects of various factors in the supply chain of Brassica vegetables including breeding, cultivation, storage and processing on intake and bioavailability of GLSs are extensively discussed in this paper.
Whole genome DNA sequencing was used to decrypt the phylogeny of multiple samples from distinct areas of cancer and morphologically normal tissue taken from the prostates of three men. Mutations were present at high levels in morphologically normal tissue distant from the cancer reflecting clonal expansions, and the underlying mutational processes at work in morphologically normal tissue were also at work in cancer. Our observations demonstrate the existence of on-going abnormal mutational processes, consistent with field-effects, underlying carcinogenesis. This mechanism gives rise to extensive branching evolution and cancer clone mixing as exemplified by the coexistence of multiple cancer lineages harboring distinct ERG fusions within a single cancer nodule. Subsets of mutations were shared either by morphologically normal and malignant tissue or between different ERG-lineages, indicating earlier or separate clonal cell expansions. Our observations inform on the origin of multifocal disease and have implications for prostate cancer therapy in individual cases.
The glucosinolates are a large group of sulphur‐containing compounds which occur in all the economically important varieties of Brassica vegetable. Their common structure comprises a β‐D‐thioglucose group, a sulphonated oxime moiety and a variable side‐chain derived from methionine, tryptophan or phenylalanine. When the plant tissue is damaged the glucosinolates are hydrolysed by the endogenous enzyme ‘myrosinase’ (thioglucoside glycohydrolase EC 3:2:3:1), to release a range of breakdown products including the bitter, biologically active isothiocyanates. Although these compounds exert antinutritional effects in animals there is also substantial evidence that they are the principal source of anticarcinogenic activity in Brassica vegetables, and this provides a strong motive for the manipulation of glucosinolate levels in vegetables for human consumption. This review provides an overview of the evidence for a beneficial role for glucosinolates in human health, and describes the current state of knowledge regarding the genetics and biosynthesis of glucosinolates, their chemical analysis, their behaviour during cooking and processing, and their bioavailability to humans. As the genetic basis of glucosinolate biosynthesis becomes more apparent, and tools for marker‐assisted plant breeding become more available, the selective breeding of horticultural brassicas with different levels and types of glucosinolates, whether by conventional means or genetic manipulation, is becoming a practical possibility. However before this strategy becomes commercially viable, the health benefits of glucosinolates for human beings must be unequivocally established. © 2000 Society of Chemical Industry
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