Sulforaphane Bioavailability and Chemopreventive Activity in Men Presenting for Biopsy of the Prostate Gland: A Randomized Controlled Trial

Abstract

Previous studies suggest compounds such as sulforaphane (SFN) derived from cruciferous vegetables may prevent prostate cancer development and progression. This study evaluated the effect of broccoli sprout extract (BSE) supplementation on blood histone deacetylase (HDAC) activity, prostate RNA gene expression, and tissue biomarkers (histone H3 lysine 18 acetylation (H3K18ac), HDAC3, HDAC6, Ki67, and p21). A total of 98 men scheduled for prostate biopsy were allocated into either BSE (200 µmol daily) or a placebo in our double-blind, randomized controlled trial. We used nonparametric tests to evaluate the differences of blood HDAC activity and prostate tissue immunohistochemistry biomarkers between treatment groups. Further, we performed RNA-Seq analysis on the prostate biopsies and identified 40 differentially expressed genes correlated with BSE treatment, including downregulation of two genes previously implicated in prostate cancer development, AMACR and ARLNC1. Although urine and plasma SFN isothiocyanates and individual SFN metabolites were statistically higher in the treatment group, our results did not show a significant difference in HDAC activity or prostate tissue biomarkers. This study indicates BSE supplementation correlates with changes in gene expression but not with several other prostate cancer biomarkers. More research is required to fully understand the chemopreventive effects of BSE supplementation on prostate cancer.

Acknowledgments

We would like to thank all of the men who contributed their time and effort to join our study. We are grateful to OHSU pathology residents who prepared prostate tissues for research. Ms. Laura Peters (VAPORHCS) assisted with subject retention and specimen collection. We acknowledge staff at the OSU Mass Spectrometry Center and the Center for Genome Research and Biocomputing at Oregon State University. We also appreciate Dr. Shannon’s research coordinator, Mrs. Amy Palma, who spent time with study subjects and worked with surgical urologists.

Statements: Our study has not been published elsewhere nor has it been submitted simultaneously for publication elsewhere.

Funding

This study was supported by the National Institute of Health (P01 CA090890 and S10RR02787801) and Oregon Agricultural Experimental Station, Hatch Funds. Clinical Trial Registration: clinicaltrials.gov identifier: NCT01265953. Protocol ID = Portland VA-09-0607.

Authors' Contribution

Jackilen Shannon, Emily Ho, and Mark Garzotto originally designed the research study; Zhenzhen Zhang and Motomi Mori conducted the biostatistical data analyses. Carmen P. Wong and Laura M. Beaver performed PCR experiments. Carmen Wong performed isothiocyanate analysis. Zhenzhen Zhang, Edward W. Davis, Carmen P. Wong, and Laura M. Beaver together wrote the initial draft of the manuscript. Mark Garzotto was the urologist who enrolled all the subjects. Wesley A. Stoller and Paige E. Farris interviewed the subjects, collected the data, coordinated, and managed the project. George V. Thomas conducted the immunohistochemistry analysis. David A. Hendrix and Edward Davis conducted RNA sequencing experiments and bioinformatics data analyses. David E. Williams and Roderick H. Dashwood critically reviewed and interpreted the results. All authors have 1) made substantial contributions to this study’s conception and design, or acquisition of data, or analysis and interpretation of data, 2) drafting or revising the whole manuscript critically, and 3) approved the submitted manuscript.