Brassica-Derived Plant Bioactives as Modulators of Chemopreventive and Inflammatory Signaling Pathways

Abstract

A high consumption of vegetables belonging to the Brassicaceae family has been related to a lower incidence of chronic diseases including different kinds of cancer. These beneficial effects of, e.g., broccoli, cabbage or rocket (arugula) intake have been mainly dedicated to the sulfur-containing glucosinolates (GLSs)—secondary plant compounds nearly exclusively present in Brassicaceae—and in particular to their bioactive breakdown products including isothiocyanates (ITCs). Overall, the current literature indicate that selected Brassica-derived ITCs exhibit health-promoting effects in vitro, as well as in laboratory mice in vivo. Some studies suggest anti-carcinogenic and anti-inflammatory properties for ITCs which may be communicated through an activation of the redox-sensitive transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2) that controls the expression of antioxidant and phase II enzymes. Furthermore, it has been shown that ITCs are able to significantly ameliorate a severe inflammatory phenotype in colitic mice in vivo. As there are studies available suggesting an epigenetic mode of action for Brassica-derived phytochemicals, the conduction of further studies would be recommendable to investigate if the beneficial effects of these compounds also persist during an irregular consumption pattern.

Effects of long-term consumption of broccoli sprouts on inflammatory markers in overweight subjects

“…The increases on broccoli metabolites were significantly related to the decreases in IL-6 and C-reactive protein levels, what suggests their implication in the modulation of these pro-inflammatory proteins. Studies on cellular models have shown that the mechanism of interaction is common in isothiocyanates and similar to that of endogenous hormones as steroids or vitamins A and D. This type of compounds possesses electrophile groups that interact with nucleophilic moieties of transcription factors, down-or up-regulating their activity [30]; it has been shown that sulphoraphane interacts with the redoxsensitive transcription factor Nrf2, to permit its translocation into the nucleus, where it binds to the antioxidant response element (ARE) and activates the synthesis of proteins related to the response to stress, as phase II detoxification enzymes and quinone reductases [31][32][33][34]. Besides, SFN inhibits activation of NF-κβ, a central transcription factor in inflammation process and the gene expression of proinflammatory mediators [34,35].…”

Brassicaceae-Derived Anticancer Agents: Towards a Green Approach to Beat Cancer

“…It has been observed that vegetable consumption is associated with a lower risk of developing cancer. Our main interest is vegetables belonging to the Brassicaceae family, such as broccoli and cauliflower, as these vegetables are a source of glucosinolates (GLs), from which other biologically active products are derived [5,6]. Unfortunately, the approach of these studies seems to be heterogeneous and not conclusive [6].…”

Sulforaphane Alters the Acidification of the Vacuole to Trigger Cell Death

“…[1, 2] Though these plants contain a diverse range of metabolites and antioxidants, the chemical agents believed to be responsible for these effects are the naturally occurring organosulfur compounds called isothiocyanates (ITCs; R-N=C=S). [3, 4]. These molecules are the products of the reaction of plant glucosinolates with myrosinase, an enzyme released by the disruption of plant tissues.…”

“…These include SFN’s abilities to inhibit phase 1 metabolizing enzymes (mostly cytochrome P450); to alter the localization of the transcription factor Nrf2 so that it can enter the nucleus to regulate the basal and inducible expression of a multitude of antioxidant proteins, detoxification enzymes, and xenobiotic transporters; and to suppress pro-inflammatory responses within the cell. [4] SFN is also known to inhibit histone deacetylase, which could explain its ability to induce cell cycle arrest and apoptosis, and to regulate different microRNAs. [11-13] Finally, there is data that suggests that SFN can trigger cell death by upregulating caspases and downregulating anti-apoptotic factors.…”