Scope Sulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults. Methods and results Subjects consumed fresh broccoli sprouts or the BSE, each providing 200 μmol SFN daily, as a single dose and as two 100-μmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ~3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21). Conclusion We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.
Epidemiological studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2-8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ (DCIS), or invasive ductal carcinoma (IDC) breast tissues. Within the supplement group, Ki-67 (p = 0.003) and HDAC3 (p = 0.044) levels significantly decreased in benign tissue. Pre-to-post-intervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (p = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.
Sulforaphane (SFN) is a phytochemical derived from cruciferous vegetables that has multiple molecular targets and anti-cancer properties. Researchers have demonstrated several chemopreventive benefits of SFN consumption, such as reductions in tumor growth, increases in cancer cell apoptosis, and disruption of signaling within tumor microenvironments both in vitro and in vivo. Emerging evidence indicates that SFN exerts several of its chemopreventive effects by altering epigenetic mechanisms. This review summarizes evidence of the impact of SFN on epigenetic events and how they relate to the chemopreventive effects of SFN observed in preclinical and clinical studies of breast and prostate cancers. Specific areas of focus include the role of SFN in the regulation of cell cycle, apoptosis, inflammation, antioxidant defense, and cancer cell signaling and their relationships to epigenetic mechanisms. Finally, remaining challenges and research needs for translating mechanistic work with SFN into human studies and clinical intervention trials are discussed.
Cruciferous vegetable components have been documented to exhibit anticancer properties. Targets of action span multiple mechanisms deregulated during cancer progression, ranging from altered carcinogen metabolism to the restoration of epigenetic machinery. Furthermore, the developing fetus is highly susceptible to changes in nutritional status and to environmental toxicants. Thus, we have exploited a mouse model of transplacental carcinogenesis to assess the impact of maternal dietary supplementation on cancer risk in offspring. In this study, transplacental and lactational exposure to a maternal dose of 15 mg/Kg B.W. of dibenzo[def,p]chrysene (DBC) resulted in significant morbidity of offspring due to an aggressive T-cell lymphoblastic lymphoma. As in previous studies, indole-3-carbinol (I3C, feed to the dam at 100, 500 or 1000 ppm), derived from cruciferous vegetables, dose-dependently reduced lung tumor multiplicity and also increased offspring survival. Brussels sprout and broccoli sprout powders, selected for their relative abundance of I3C and the bioactive component sulforaphane (SFN), respectively, surprisingly enhanced DBC-induced morbidity and tumorigenesis when incorporated into the maternal diet at 10% wt/wt. Purified SFN, incorporated in the maternal diet at 400 ppm, also decreased the latency of DBC-dependent morbidity. Interestingly, I3C abrogated the effect of SFN when the two purified compounds were administered in equimolar combination (500 ppm I3C and 600 ppm SFN). SFN metabolites measured in the plasma of neonates positively correlated with exposure levels via the maternal diet but not with offspring mortality. These findings provide justification for further study of the safety and bioactivity of cruciferous vegetable phytochemicals at supplemental concentrations during the perinatal period.
Objective: To examine the relationship between dietary cruciferous vegetable intake and selected tumour biomarkers for histone acetylation (H3K9ac, H3K18ac, HDAC3 and HDAC6), proliferation (Ki-67) and cell-cycle regulation (p21) from breast tissue. Design: The study used baseline data of women recruited to participate in a clinical trial of sulforaphane supplement. Dietary cruciferous vegetable intake was collected through a validated Arizona Cruciferous Vegetable Intake Questionnaire. Breast tissue was obtained from biopsy samples. Spearman correlations were calculated between intake of specific cruciferous vegetables and biomarkers. Tissue biomarkers were log 2 -transformed to obtain approximate normality. Linear regression analyses were conducted to examine associations between cruciferous vegetable intake and biomarkers adjusting for age and use of non-steroidal anti-inflammatory drugs. False discovery rate (FDR) was used to account for multiple comparisons. Setting: Clinical trial baseline. Subjects: Fifty-four women who had abnormal mammogram findings and were scheduled for breast biopsy. Results: Mean intake of total cruciferous vegetables from all food sources was 81·7 (SD 57·3) g/d. Mean urinary total sulforaphane metabolites was 0·08 (SD 0·07) µM/mM creatinine. Total cruciferous vegetable intake was inversely associated with Ki-67 protein expression in breast ductal carcinoma in situ (DCIS) tissue (β = − 0·004; SE = 0·001; FDR q value = 0·03), but not in benign or invasive ductal carcinoma (IDC) tissue. No association was found for other biomarkers measured (HDAC3, HDAC6, H3K9, H3K18 and p21) in all tissues examined (benign, DCIS and IDC). Conclusions: The present study sought to provide additional evidence for the potential role of sulforaphane in histone acetylation and cell proliferation. Here, we report that total cruciferous vegetable intake is associated with decreased cell proliferation in breast DCIS tissue. Keywords Cruciferous vegetables Biomarkers Breast tissueBreast cancer is the most prevalent cancer and the most common cause of death from cancer in women in the USA (1) . In 2013, approximately 21 % of newly diagnosed breast cancer cases were in situ breast cancer with 85 % of them as ductal carcinoma in situ (DCIS) (2) . DCIS starts with abnormal breast changes in the ductal cells and more than one-third of cases will develop into invasive cancer (2) . The progression from normal tissue to DCIS and to invasive cancer depends on many risk factors. Beyond conventional surgical treatment and neoadjuvant therapy, women with breast cancer often attempt to seek alternative treatment to improve outcomes. A report in 2002 showed that 63-83 % of breast cancer patients used at least one type of complementary and alternative medicine to prevent the development or progression of breast cancer (3) . Nutritional and dietary intake modifications were among the most commonly used complementary and alternative medicines (3) . Dietary factors, especially higher vegetable intake, appear to be associ...
Sulforaphane (SFN), an isothiocyanate derived from cruciferous vegetables, has many potential health benefits including cancer prevention. There has been intense study of the molecular and genetic targets of SFN, however, there is limited knowledge around the biological pathways it targets in humans. This study's objective was to identify examine metabolomic profiles in healthy adult before and after consuming fresh broccoli sprouts, a rich and bioavailable dietary source of SFN, to observe how multiple metabolites respond to SFN consumption in vivo. Twenty healthy adults consumed 200 µmol SFN equivalents from fresh broccoli sprouts and provided blood samples at time 0, 3, 6, 12, 24 and 48 hours following consumption. Untargeted metabolomic analysis was performed on plasma samples from each time point using an AB Sciex TripleTOF® 5600 coupled to a Shimadzu ultra‐high performance liquid chromatography system. Following sprout intake, altered levels for metabolites associated with steroid, lipid and protein metabolism, the urea cycle, nucleotide and one‐carbon metabolism, and glutathione synthesis were observed. This research provides important information on novel molecular targets and mechanisms of SFN that can improve understanding of SFN's role in health and disease prevention. R01CA122906, P01CA090890, P30 ES000210
Sulforaphane (SFN) is an isothiocyanate derived from cruciferous vegetables with many potential health benefits. However, there is limited knowledge about its bioavailability in humans. Crucifers contain glucoraphanin (GFN), which is hydrolyzed by myrosinase to yield SFN. Myrosinase is present within the plant, and a small amount is produced by gut bacteria. We previously observed a 7‐ fold decrease in SFN bioavailability from GFN supplements with inactivated myrosinase than from fresh broccoli sprouts, suggesting that the lack of myrosinase impacts SFN bioavailability. Goals of the present study were to determine the bioavailability and bioactivity of a myrosinase‐treated broccoli sprout extract (BSE) supplement and broccoli sprouts. Participants consumed BSEs or broccoli sprouts once or twice a day (time 0 and 12h). SFN bioavailability from BSE was improved over myrosinase‐inactivated GFN supplements but was still about 3 times lower than broccoli sprouts. Consuming SFN twice daily maintained plasma metabolite levels at 24 hours, suggesting that the twice daily dosing protocol resulted in longer retention of plasma SFN levels. Nrf‐2 target genes and histone deacetylase activity were used to measure biological response to SFN treatment. This research provides important information for SFN supplement use in clinical trials. Funding: R01CA122906 & P01CA090890Grant Funding Source: R01CA122906, P01CA090890
<p>Supplementary Table 1. Basic characteristics of women in the study Supplementary Table 2. Incidence of reported grade 2 adverse events in the BroccoMax{trade mark, serif} trial (treatment-related) Supplementary Table 3. Sulforaphane (SFN) and SFN metabolite levels in urine and plasma as well as histone deacetylase (HDAC) activity changes from pre- to post-treatment by treatment group Supplementary Table 4. Log2-transformed LSMEANS of immunohistochemistry H-score of selected breast tissue biomarkers in women scheduled for breast biopsy participating the BroccoMax{trade mark, serif} trial</p>
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