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A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer.

ABSTRACT: Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells.Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforaphane inhibits AR signaling in prostate cancer cells. Here, we report results from the first clinical trial of sulforaphane-rich extracts in men with prostate cancer.We treated 20 patients who had recurrent prostate cancer with 200 ?moles/day of sulforaphane-rich extracts for a maximum period of 20 weeks and determined the proportion of patients with ?50% PSA declines, the primary endpoint. Only one subject experienced a ?50% PSA decline. Thus, the primary endpoint was not achieved. Seven patients experienced smaller PSA declines (<50%). There was also a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p?=?0.044)]. Finally, treatment with sulforaphane-rich extracts was safe with no Grade 3 adverse events.Treatment with 200 ?moles/day of sulforaphane-rich extracts did not lead to ?50% PSA declines in the majority of patients. However, because of the safety of treatment and the effects on PSADT modulation, further studies, including those with higher doses, may be warranted to clarify the role of sulforaphane as a prevention agent or treatment agent.

SUBMITTER: Alumkal JJ

PROVIDER: S-EPMC4390425 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer.

Alumkal Joshi J JJ Slottke Rachel R Schwartzman Jacob J Cherala Ganesh G Munar Myrna M Graff Julie N JN Beer Tomasz M TM Ryan Christopher W CW Koop Dennis R DR Gibbs Angela A Gao Lina L Flamiatos Jason F JF Tucker Erin E Kleinschmidt Richard R Mori Motomi M

Investigational new drugs 20141129 2

<h4>Introduction</h4>Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells.<h4>Purpose</h4>Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforap ...[more]

PMID: 25431127

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Project description:The generation of oxidative stress by ambient air pollution particles contributes to the development of allergic sensitization and asthma, as demonstrated by intranasal challenge with well-characterized diesel exhaust particle (DEP) suspensions in humans. This effect is due to the presence of redox active organic chemicals in DEP, and can be suppressed by antioxidants and inducers of phase II enzymes in animals. In this communication, we determined whether the administration of a standardized broccoli sprout extract (BSE), which contains a reproducible amount of the sulforaphane (SFN) precursor, glucoraphanin, could be used to suppress the nasal inflammatory response in human subjects challenged with 300 μg of an aqueous DEP suspension (equivalent to daily PM exposure levels on a Los Angeles freeway). SFN is capable of inducing an antioxidant and phase II response via activation of the nuclear transcription factor (erythroid-derived 2)-like 2 (Nrf2). Previous studies have shown that 70-90% SFN delivered by BSE is absorbed, metabolized, and excreted in humans. An initial intranasal challenge with DEP in 29 human subjects was used to characterize the magnitude of the inflammatory response. Following a 4 week washout, a BSE that delivers a reproducible and standardized dose of 100 μmol SFN in mango juice was administered daily for four days. The nasal DEP challenge was repeated and lavage fluid collected to perform white blood cell (WBC) counts. The average nasal WBC increased by 66% over the initial screening levels and by 85% over the control levels 24 hours after DEP exposure. However, total cell counts decreased by 54% when DEP challenge was preceded by daily BSE administration for 4 days (p < 0.001). Since the SFN dose in these studies is equivalent to the consumption of 100-200 g broccoli, our study demonstrates the potential preventive and therapeutic potential of broccoli or broccoli sprouts rich in glucoraphanin for reducing the impact of particulate pollution on allergic disease and asthma.

Project description:BackgroundEpidemiological 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.ObjectiveWe 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.MethodsForty-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.ResultsIn 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.ConclusionConsuming 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.

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A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer.

Publications

A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer.

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