Chemoprevention of Prostate Cancer, HDAC Inhibition and DNA Methylation

Prostate cancer is the most frequently diagnosed non-cutaneous cancer and is the second
leading cause of cancer death in American men. The precise etiologic factors that initiate
and enhance the progression of prostate cancer remain unknown, but epigenetic alterations and
diet/lifestyle factors have come forth as significant contributing factors. Epidemiologic
studies suggest that cruciferous vegetable intake decreases the risk for prostate cancer. The
long-term goal of this proposal is to identify mechanisms by which dietary compounds, such as
those found in cruciferous vegetables decrease prostate cancer risk. The objective of the
study is to identify mechanisms by which compounds found in cruciferous vegetables alter gene
expression via epigenetic modifications and may prevent prostate cancer development.

The investigators have found that SFN, an isothiocyanate found in cruciferous vegetables,
inhibits HDAC activity in human colorectal and prostate cancer cells.

Targeting the epigenome, including the use of HDAC and DNA methyltransferase (DNMT)
inhibitors, is an evolving strategy for cancer chemoprevention and both have shown promise in
cancer clinical trials.

This Randomized, Double Blind, Clinical Trial will address the following objectives:

1. Identify distribution of SFN and its metabolites and HDAC inhibition following SFN
supplementation in subjects at risk for prostate cancer (Primary Endpoints)

2. Investigate the effects of broccoli sprout supplementation on DNA methylation status and
proliferation markers in a pre-biopsy setting (secondary analysis)

The effects of short-term SFN supplementation on benign epithelial tissue will be studied in
men characterized as being at risk for prostate cancer in a randomized, placebo-controlled
trial. Men scheduled for prostate biopsy will be recruited into the trial.

Following successful completion of the consent, two 10 mL blood specimens for study analyses,
a 4 mL specimen for total bilirubin assessment will be drawn and the subject will provide a
urine sample. The study coordinator will explain the Diet History questionnaires (DHQ) and
administer the risk factor and adverse event (AE) questionnaires in order to obtain data on
potential confounding dietary variables and gain subjects' baseline symptoms.

The study coordinator will provide the subject with a four-week supply of either SFN
glucosinolate capsules or matching placebo, as dispensed by the Research Pharmacy.

Around every 2 weeks, study coordinator will call to complete AE reporting and any changes in
medications or supplements and complete brief cruciferous vegetable intake checklist.
Subjects will return any unused study "drug" to the study coordinator at the time of biopsy
(or at the 4 week visit if subject's prostate biopsy is delayed).

Inclusion Criteria:

- Men scheduled for a prostate biopsy

- Age 21 years or older

- Signed informed subject consent

Exclusion Criteria:

- Definitive diagnosis with prostate cancer

- Significant active medical illness which in the opinion of the investigator or
clinician would preclude protocol treatment

- Diagnosis of liver disease as noted on the patient problem list or baseline total
bilirubin greater than institutional upper limit of normal

- Subject reported allergy or sensitivity to cruciferous vegetables

- Use of oral antibiotics, with the exception of doxycycline, within three months prior
to randomization

- Use of warfarin or need for therapeutic anticoagulation at time of biopsy or at
anytime during the course of the trial.

- Current oral steroid therapy

- Current therapy with valproate or other pharmacological drugs associated with HDAC
inhibition

- Diagnosed dementia as noted on the patient problem list or other significant mental
illness that may impact the subjects' ability to follow instructions or comply with
the study protocol

- Patient may not be a part of another flagged study

- Patients already taking SFN dietary supplements