Abstract We have previously shown that broccoli sprouts are a rich source of chemopreventive isothiocyanates, which potently induce carcinogen-detoxifying enzymes and inhibit the development of mammary and skin tumors in rodents. However, the principal isothiocyanate present in broccoli sprout extracts, sulforaphane, not only induces carcinogen-detoxifying enzymes but also activates apoptosis and blocks cell cycle progression. In this article, we show that an aqueous extract of broccoli sprouts potently inhibits the growth of human bladder carcinoma cells in culture and that this inhibition is almost exclusively due to the isothiocyanates. Isothiocyanates are present in broccoli sprouts as their glucosinolate precursors and blocking their conversion to isothiocyanates abolishes the antiproliferative activity of the extract. Moreover, the potency of isothiocyanates in the extract in inhibiting cancer cell growth was almost identical to that of synthetic sulforaphane, as judged by their IC50 values (6.6 versus 6.8 μmol/L), suggesting that other isothiocyanates in the extract may be biologically similar to sulforaphane and that nonisothiocyanate substances in the extract may not interfere with the antiproliferative activity of the isothiocyanates. Further study showed that the isothiocyanate extract of broccoli sprouts activated the mitochondria-mediated apoptosis pathway and halted cells in S and M phases. Cell cycle arrest was associated with down-regulation of Cdc25C and disruption of mitotic spindles. These data show that broccoli sprout isothiocyanate extract is a highly promising substance for cancer prevention/treatment and that its antiproliferative activity is exclusively derived from isothiocyanates. [Mol Cancer Ther 2006;5(4):935–44]
Abstract Glucosinolates (GS) are metabolized to isothiocyanates that may enhance human healthspan by protecting against a variety of chronic diseases. Moringa oleifera , the drumstick tree, produces unique GS but little is known about GS variation within M . oleifera , and even less in the 12 other Moringa species, some of which are very rare. We assess leaf, seed, stem, and leaf gland exudate GS content of 12 of the 13 known Moringa species. We describe 2 previously unidentified GS as major components of 6 species, reporting on the presence of simple alkyl GS in 4 species, which are dominant in M . longituba . We document potent chemoprotective potential in 11 of 12 species, and measure the cytoprotective activity of 6 purified GS in several cell lines. Some of the unique GS rank with the most powerful known inducers of the phase 2 cytoprotective response. Although extracts of most species induced a robust phase 2 cytoprotective response in cultured cells, one was very low ( M . longituba ), and by far the highest was M . arborea , a very rare and poorly known species. Our results underscore the importance of Moringa as a chemoprotective resource and the need to survey and conserve its interspecific diversity.
Broccoli sprouts are a rich source of glucosinolates and isothiocyanates that induce phase 2 detoxication enzymes, boost antioxidant status, and protect animals against chemically induced cancer. Glucosinolates are hydrolyzed by myrosinase (an enzyme found in plants and bowel microflora) to form isothiocyanates. In vivo , isothiocyanates are conjugated with glutathione and then sequentially metabolized to mercapturic acids. These metabolites are collectively designated dithiocarbamates. We studied the disposition of broccoli sprout glucosinolates and isothiocyanates in healthy volunteers. Broccoli sprouts were grown, processed, and analyzed for ( a ) inducer potency; ( b ) glucosinolate and isothiocyanate concentrations; ( c ) glucosinolate profiles; and ( d ) myrosinase activity. Dosing preparations included uncooked fresh sprouts (with active myrosinase) as well as homogenates of boiled sprouts that were devoid of myrosinase activity and contained either glucosinolates only or isothiocyanates only. In a crossover study, urinary dithiocarbamate excretion increased sharply after administration of broccoli sprout glucosinolates or isothiocyanates. Cumulative excretion of dithiocarbamates following 111-μmol doses of isothiocyanates was greater than that after glucosinolates (88.9 ± 5.5 and 13.1 ± 1.9 μmol, respectively; P < 0.0003). In subjects fed four repeated 50-μmol doses of isothiocyanates, the intra- and intersubject variation in dithiocarbamate excretion was very small (coefficient of variation, 9%), and after escalating doses, excretion was linear over a 25- to 200-μmol dose range. Dithiocarbamate excretion was higher when intact sprouts were chewed thoroughly rather than swallowed whole (42.4 ± 7.5 and 28.8 ± 2.6 μmol; P = 0.049). These studies indicate that isothiocyanates are about six times more bioavailable than glucosinolates, which must first be hydrolyzed. Thorough chewing of fresh sprouts exposes the glucosinolates to plant myrosinase and significantly increases dithiocarbamate excretion. These findings will assist in the design of dosing regimens for clinical studies of broccoli sprout efficacy.
Abstract The isothiocyanate sulforaphane was isolated from broccoli extracts in a bioactivity-guided fractionation as the principal and very potent inducer of cytoprotective phase 2 enzymes and subsequently shown to inhibit tumor development in animal models that involve various carcinogens and target organs. Because broccoli and broccoli sprouts are widely consumed, extracts obtained from them are viewed as convenient vehicles for sulforaphane delivery to humans. In relation to our current interest in devising strategies for protection against UV light–induced skin cancer, it was necessary to examine the safety and efficacy of topical application of sulforaphane-containing broccoli sprout extracts as single and multiple doses in both mice and humans. Topical application of an extract delivering 100 nmol sulforaphane/cm2 increased the protein levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione S-transferase A1, and heme oxygenase 1, three representative phase 2 enzymes, in mouse skin epidermis. Quantitative assessment of the activity of NQO1 24 h after dosing showed increases of 1.5- and 2.7-fold after application of single and multiple (thrice, every 24 h) doses, respectively. A dose-escalation safety study in healthy human subjects revealed no adverse reactions when doses as high as 340 nmol of sulforaphane in the form of broccoli sprout extracts were applied topically to the center of a 1-cm-diameter circle drawn on the volar forearm. A subsequent efficacy study showed that despite the interindividual differences in basal levels, the enzyme activity of NQO1 in homogenates of 3-mm full thickness skin punch biopsies increased in a dose-dependent manner, with maximum increases of 1.5- and 4.5-fold after application of 150 nmol doses, once or three times (at 24 h-intervals), respectively, thus providing direct evidence for induction of the phase 2 response in humans. (Cancer Epidemiol Biomarkers Prev 2007;16(4):847–51)
Taste drives consumption of foods. The tropical tree Moringa oleifera is grown worldwide as a protein-rich leafy vegetable and for the medicinal value of its phytochemicals, in particular its glucosinolates, which can lead to a pronounced harsh taste. All studies to date have examined only cultivated, domestic variants, meaning that potentially useful variation in wild type plants has been overlooked. We examine whether domesticated and wild type M. oleifera differ in myrosinase or glucosinolate levels, and whether these different levels impact taste in ways that could affect consumption. We assessed taste and measured levels of protein, glucosinolate, myrosinase content, and direct antioxidant activity of the leaves of 36 M. oleifera accessions grown in a common garden. Taste tests readily highlighted differences between wild type and domesticated M. oleifera. There were differences in direct antioxidant potential, but not in myrosinase activity or protein quantity. However, these two populations were readily separated based solely upon their proportions of the two predominant glucosinolates (glucomoringin and glucosoonjnain). This study demonstrates substantial variation in glucosinolate composition within M. oleifera. The domestication of M. oleifera appears to have involved increases in levels of glucomoringin and substantial reduction of glucosoonjnain, with marked changes in taste.
The tropical tree Moringa oleifera produces high yields of protein-rich leaf biomass, is widely used as a food source, contains an abundance of phytochemicals, and thus has great potential for chronic disease prevention and perhaps, treatment. We have developed and characterized standardized ways of preparing aqueous “teas” from moringa leaves to deliver precisely calibrated levels of phytochemicals for use in clinical trials. These phytochemicals, especially the glucosinolate glucomoringin and the isothiocyanate moringin, produced from it following hydrolysis by the enzyme myrosinase, provide potent anti-inflammatory and cytoprotective indirect antioxidant activity. The taste of both hot and cold teas is palatable without the need for flavor masking. These teas can be easily and reproducibly prepared in underserved tropical regions of the world where moringa is cultivated. Isothiocyanate yield from a cold extraction was rapid and essentially complete after 30 min and its anti-inflammatory potential is comparable to that of equimolar purified moringin. A preparation similar to this may be safe to consume with respect to its bacterial titer even after 48 h without refrigeration. Thus, facile delivery of moringa tea to both adults and children for clinical evaluation of their effects on such conditions as autism, diabetes, and hypertension, is now possible.
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