Watercress supplementation in diet reduces lymphocyte DNA damage and alters blood antioxidant status in healthy adults.
BACKGROUND: Cruciferous vegetable (CV) consumption is associated with a reduced risk of several cancers in epidemiologic studies. OBJECTIVE: The aim of this study was to determine the effects of watercress (a CV) supplementation on biomarkers related to cancer risk in healthy adults. DESIGN: A single-blind, randomized, crossover study was conducted in 30 men and 30 women (30 smokers and 30 nonsmokers) with a mean age of 33 y (range: 19-55 y). The subjects were fed 85 g raw watercress daily for 8 wk in addition to their habitual diet. The effect of supplementation was measured on a range of endpoints, including DNA damage in lymphocytes (with the comet assay), activity of detoxifying enzymes (glutathione peroxidase and superoxide dismutase) in erythrocytes, plasma antioxidants (retinol, ascorbic acid, alpha-tocopherol, lutein, and beta-carotene), plasma total antioxidant status with the use of the ferric reducing ability of plasma assay, and plasma lipid profile. RESULTS: Watercress supplementation (active compared with control phase) was associated with reductions in basal DNA damage (by 17%; P = 0.03), in basal plus oxidative purine DNA damage (by 23.9%; P = 0.002), and in basal DNA damage in response to ex vivo hydrogen peroxide challenge (by 9.4%; P = 0.07). Beneficial changes seen after watercress intervention were greater and more significant in smokers than in nonsmokers. Plasma lutein and beta-carotene increased significantly by 100% and 33% (P < 0.001), respectively, after watercress supplementation. CONCLUSION: The results support the theory that consumption of watercress can be linked to a reduced risk of cancer via decreased damage to DNA and possible modulation of antioxidant status by increasing carotenoid concentrations.
Am J Clin Nutr. 2007 Feb;85(2):504-10
Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines.
Sulforaphane, an isothiocyanate found in cruciferous vegetables, has been shown to induce phase 2 detoxication enzymes and inhibit the growth of chemically induced mammary tumors in rats, although the exact mechanisms of action of sulforaphane are not understood. In this study, we evaluated the effects of sulforaphane on cell growth and death in several human breast cancer cell lines and examined the hypothesis that sulforaphane acts as a histone deacetylase (HDAC) inhibitor in these cell lines. Sulforaphane treatment inhibited cell growth, induced a G(2)-M cell cycle block, increased expression of cyclin B1, and induced oligonucleosomal DNA fragmentation in the four human breast cancer cell lines examined, MDA-MB-231, MDA-MB-468, MCF-7, and T47D cells. Activation of apoptosis by sulforaphane in MDA-MB-231 cells seemed to be initiated through induction of Fas ligand, which resulted in activation of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, whereas apoptosis in the other breast cancer cell lines was initiated by decreased Bcl-2 expression, release of cytochrome c into the cytosol, activation of caspase-9 and caspase-3, but not caspase-8, and poly(ADP-ribose) polymerase cleavage. Sulforaphane inhibited HDAC activity and decreased the expression of estrogen receptor-alpha, epidermal growth factor receptor, and human epidermal growth factor receptor-2 in each cell line, although no change in the acetylation of H3 or H4 was seen. These data suggest that sulforaphane inhibits cell growth, activates apoptosis, inhibits HDAC activity, and decreases the expression of key proteins involved in breast cancer proliferation in human breast cancer cells. These results support testing sulforaphane in vivo and warrant future studies examining the clinical potential of sulforaphane in human breast cancer.
Mol Cancer Ther. 2007 Mar;6(3):1013-21
Cruciferous vegetables and human cancer risk: epidemiologic evidence and mechanistic basis.
Cruciferous vegetables are a rich source of glucosinolates and their hydrolysis products, including indoles and isothiocyanates, and high intake of cruciferous vegetables has been associated with lower risk of lung and colorectal cancer in some epidemiological studies. Glucosinolate hydrolysis products alter the metabolism or activity of sex hormones in ways that could inhibit the development of hormone-sensitive cancers, but evidence of an inverse association between cruciferous vegetable intake and breast or prostate cancer in humans is limited and inconsistent. Organizations such as the National Cancer Institute recommend the consumption of five to nine servings of fruits and vegetables daily, but separate recommendations for cruciferous vegetables have not been established. Isothiocyanates and indoles derived from the hydrolysis of glucosinolates, such as sulforaphane and indole-3-carbinol (I3C), have been implicated in a variety of anticarcinogenic mechanisms, but deleterious effects also have been reported in some experimental protocols, including tumor promotion over prolonged periods of exposure. Epidemiological studies indicate that human exposure to isothiocyanates and indoles through cruciferous vegetable consumption may decrease cancer risk, but the protective effects may be influenced by individual genetic variation (polymorphisms) in the metabolism and elimination of isothiocyanates from the body. Cooking procedures also affect the bioavailability and intake of glucosinolates and their derivatives. Supplementation with I3C or the related dimer 3,3’-diindolylmethane (DIM) alters urinary estrogen metabolite profiles in women, but the effects of I3C and DIM on breast cancer risk are not known. Small preliminary trials in humans suggest that I3C supplementation may be beneficial in treating conditions related to human papilloma virus infection, such as cervical intraepithelial neoplasia and recurrent respiratory papillomatosis, but larger randomized controlled trials are needed.
Pharmacol Res. 2007 Mar;55(3):224-36
Head and neck cancer: a case for inhibition by isothiocyanates and indoles from cruciferous vegetables.
Chemical carcinogens derived from cigarettes and other tobacco products, as well as betel quid, paan, and alcohol consumption, are commonly associated with head and neck cancer risk. This is a particularly debilitating cancer, with a high recurrence rate and long-term treatment comorbidities affecting health and lifestyle. Controlling tobacco access or use may be an ideal prevention strategy but may also be challenging or undesired. Individuals, however, may be able to reduce their risk through simple and focused dietary change. Results from epidemiologic studies, basic research, and clinical investigations suggest that a diet rich in cruciferous vegetables may increase carcinogen metabolism, induce apoptosis, and reduce the risk of developing a primary head and neck tumor. This review briefly summarizes head and neck cancer nutritional epidemiology, and then describes the biochemical and epidemiologic literature describing the effects of crucifer consumption on head and neck carcinogenesis. To translate these findings, the strengths and limitations of specific intervention models are discussed, including differences in target populations and the choice of a food-based or pill-based approach for intervention. Addressing these factors in a future intervention may define a low-cost and non-toxic approach to reduce the burden of head and neck cancer.
Eur J Cancer Prev. 2007 Aug;16(4):348-56
Phenethyl isothiocyanate, a cancer chemopreventive constituent of cruciferous vegetables, inhibits cap-dependent translation by regulating the level and phosphorylation of 4E-BP1.
Phenethyl isothiocyanate (PEITC), a constituent of many edible cruciferous vegetables, exerts significant protection against chemically induced cancer in animal models and inhibits growth of cancer cells in culture and in vivo by causing cell cycle arrest and apoptosis induction. In this study, we report a novel response to PEITC involving the regulation of translation initiation at pharmacologically achievable concentrations. Treatment of human colorectal cancer HCT-116 cells and human prostate cancer PC-3 cells, but not a normal prostate epithelial cell line (PrEC), with PEITC caused an increase in expression of the eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) and inhibition of 4E-BP1 phosphorylation. Results from pull-down assay using 7-methyl-GTP Sepharose 4B beads indicated that PEITC treatment reduced cap-bound eIF4E, confirming that increased 4E-BP1 expression and inhibition of 4E-BP1 phosphorylation indeed reduced the availability of eIF4E for translation initiation. Accordingly, results from in vivo translation using luciferase reporter assay indicated that PEITC treatment inhibited cap-dependent translation, in particular the translation of mRNA with secondary structure (stem-loop structure). Ectopic expression of eIF4E prevented PEITC-induced translation inhibition and conferred significant protection against PEITC-induced apoptosis. These results indicate that PEITC modulates availability of eIF4E for translation initiation leading to inhibition of cap-dependent translation. The present study also suggests that inhibition of cap-dependent translation may be an important mechanism in PEITC-induced apoptosis.
Cancer Res. 2007 Apr 15;67(8):3569-73