Transcriptional changes in prostate of men on active surveillance after a 12-mo glucoraphanin-rich broccoli intervention—results from the Effect of Sulforaphane on prostate CAncer PrEvention (ESCAPE) randomized controlled trial

Abstract

Background Epidemiological evidence suggests that consumption of cruciferous vegetables is associated with reduced risk of prostate cancer progression, largely attributed to the biological activity of glucosinolate degradation products, such as sulforaphane derived from glucoraphanin. Because there are few therapeutic interventions for men on active surveillance for prostate cancer to reduce the risk of cancer progression, dietary approaches are an appealing option for patients. Objective We evaluated whether consumption of a glucoraphanin-rich broccoli soup for 1 y leads to changes in gene expression in prostate tissue of men with localized prostate cancer. Methods Forty-nine men on active surveillance completed a 3-arm parallel randomized double-blinded intervention study for 12 mo and underwent transperineal template biopsy procedures and dietary assessment at the start and end of the study. Patients received a weekly 300 mL portion of soup made from a standard broccoli (control) or from 1 of 2 experimental broccoli genotypes with enhanced concentrations of glucoraphanin, delivering 3 and 7 times that of the control, respectively. Gene expression in tissues from each patient obtained before and after the dietary intervention was quantified by RNA sequencing followed by gene set enrichment analyses. Results In the control arm, there were several hundred changes in gene expression in nonneoplastic tissue during the 12 mo. These were associated with an increase in expression of potentially oncogenic pathways including inflammation processes and epithelial–mesenchymal transition. Changes in gene expression and associated oncogenic pathways were attenuated in men on the glucoraphanin-rich broccoli soup in a dose-dependent manner. Although the study was not powered to assess clinical progression, an inverse association between consumption of cruciferous vegetables and cancer progression was observed. Conclusion Consuming glucoraphanin-rich broccoli soup affected gene expression in the prostate of men on active surveillance, consistent with a reduction in the risk of cancer progression. This trial was registered at clinicaltrials.gov as NCT01950143.

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

“…Finally, we proceeded with the analysis of the articles studying long-term interventions (Table S3). In these works, we found various publications on different types of cancers: prostate [48,49], breast [37], ovarian [50], and pancreas (pilot [51] and development [52]), and one work on type 2 diabetes mellitus [35] and a letter to the editor [38] as a result of this study.…”

“…The works of Paltsev et al [48] and Traka et al [49] were both dedicated to prostate cancer, for a period of 12 months, but with different interventions and different parameters of the stage of development. In the first one [48], the intervention was carried out using capsules with 900 mg of DIM (3,3-diindolylmethane) and considered data of morphological changes (MI formula to calculate presence of cancer) in the prostate, and registration of the prostatic intraepithelial neoplasias (PIN) of low and high degree as well as the number of foci of cancer and urological dynamic parameters (maximum, average, and residual urinary flow) and erectile function.…”

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

“…Recently, it was found that the consumption of glucoraphanin-rich broccoli soup affects gene expression in the prostates of men on active surveillance, consistent with a reduction in the risk of cancer progression [47]. Broccoli sprouts are considered a functional food as they are naturally enriched in glucoraphanin (GR), which is the biological precursor of sulforaphane (SFN), a compound mainly found in broccoli sprouts, Chinese kale, cabbage, and watercress.…”

MicroRNAs as novel targets of sulforaphane in cancer therapy: The beginning of a new tale?

“…In terms of antitumor activity, sulforaphane has shown great potential for treatment of cancers such as bladder cancer (Xia, Kang, Jung, Zhang, & Lian, ), colon cancer (Darkwa, Burkhardt, & Tsuji, ), triple negative breast cancer (Jensen, Slattery, Housley, & Hansen, ), pancreatic cancer (Yin et al, ), prostate cancer (Traka et al, ), and non‐small cell lung cancer (Zheng et al, ). Although high numbers of studies have investigated the antitumor activity of sulforaphane, there is a need for a precise review to describe the mechanism of antitumor activity of sulforaphane.…”

“…In terms of antitumor activity, sulforaphane has shown great potential for treatment of cancers such as bladder cancer (Xia, Kang, Jung, Zhang, & Lian, 2019), colon cancer (Darkwa, Burkhardt, & Tsuji, 2019), triple negative breast cancer (Jensen, Slattery, Housley, & Hansen, 2019), pancreatic cancer (Yin et al, 2019), prostate cancer (Traka et al, 2019), and non-small cell lung cancer .…”