Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy

Abstract

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.

The Role of Brassica Bioactives on Human Health: Are We Studying It the Right Way?

“…In both studies, the time for the intervention was similar, namely 20 and 24 weeks, respectively, but the amount of SFN was much higher in the work of Cipolla et al [46], and that probably favored the better more encouraging final results in this study. In any case, Atwell et al [47] planned to evaluate the efficacy of the consumption of the broccoli sprouts extract to modify the activity of the HDAC (histone deacetylase) and the breast tumor marker CA (carcinogenic antigen) in order to improve the diagnosis in women with benign disease and non-invasive CA. They proposed an intervention using six pills with a theoretical content of SFN of 30 mg in three administrations per day.…”

Sulforaphane absorption and histone deacetylase activity following single dosing of broccoli sprout supplement in normal dogs

“…On Day 0 of the study, dogs were orally administered three capsules of a broccoli sprout supplement (BroccoMax TM ) to achieve 90 mg total of GFN (per Jarrow Formulas â , 30 mg of GFN yields 8 mg SFN in vitro). The GFN dose used was based on estimated weight equivalent dose in people (Atwell et al 2015a). All dogs swallowed the supplement without chewing, and received their morning meal immediately following the broccoli sprout supplement dosing (BroccoMax TM ).…”

Small-molecule modulators of PXR and CAR

“…Moreover, a recent human clinical study suggested that this compound was not an effective antagonist of the hPXR in vivo [43]. Considering the antagonistic effect on PXR of SFN at relative high concentrations in vitro and its other pharmacologic activities, such as histone deacetylase inhibition [44], achieved at relatively lower concentrations, further investigation of the on-target effect of SFN against PXR is warranted, especially at physiologically relevant concentrations.…”