# Biomarkers of Sulforaphane/Broccoli Sprout Extract in Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $480,187

## Abstract

ABSTRACT
Scientific Premise and Hypothesis: Chemoprevention using safe and inexpensive phytochemicals from edible
or medicinal plants is appealing for reducing the death and suffering from prostate cancer, which continues to
be a leading cause of cancer-linked mortality among American men. A chemopreventative intervention for
prostate cancer is still lacking. Increased de novo synthesis coupled with β-oxidation of fatty acids is a rather
unique and targetable mechanism of human prostate cancer. A role for upregulated de novo fatty acid synthesis
in pathogenesis of prostate cancer is substantiated by studies showing overexpression of mRNA/protein levels
of key fatty acid synthesis enzymes, including ATP citrate lyase (ACLY), acetyl-CoA carboxylase 1 (ACC1),
and/or fatty acid synthase (FASN) in early (prostatic intraepitheilial neoplasia; PIN) as well as advanced
(adenocarcinoma) disease when compared to normal tissue. In addition, genetic or pharmacological suppression
of ACLY, ACC1, and FASN causes inhibition of prostate cancer cell growth in vitro and in vivo. Therefore,
inhibition of synthesis and/or β-oxidation of fatty acids represents a promising strategy for chemoprevention of
prostate cancer. The overall goal of this bench-cage-bedside project is to determine the feasibility of fatty acid
metabolism inhibition for chemoprevention of prostate cancer using sulforaphane (SFN), which is the principal
bioactive phytochemical in broccoli sprout extract (BSE). The preclinical studies are conceived to test the
hypothesis that prostate cancer chemoprevention by SFN and BSE in a clinically-relevant transgenic
mouse model (Hi-Myc) is associated with suppression of synthesis as well as β-oxidation of fatty acids
leading to inhibition of cancer cell proliferation. A pilot double-blind, randomized, and placebo-controlled
window of opportunity clinical trial in men scheduled for prostatectomy is also proposed to determine whether
daily oral administration of a well-characterized BSE formulation (BroccoMax®), the safety of which has already
been tested clinically, for 4 weeks leads to suppression of circulating and prostate tumor levels of fatty acids.
Support for the above stated hypothesis derives from our own published and preliminary unpublished findings.
Specifically, we found that SFN treatment not only suppresses protein/mRNA levels of ACC1 and FASN as well
as the dehydrogenases implicated in β-oxidation of fatty acids but also decreases acetyl-CoA levels in human
prostate cancer cells in vitro and prostate tumors of TRAMP mice in vivo. Acetyl-CoA is the building block of de
novo fatty acid synthesis but is also generated in the mitochondria upon β-oxidation of fatty acids.
Specific Aims: The well-integrated specific aims of this highly-focused application are to: (1) Determine the
mechanism underlying SFN-mediated inhibition of fatty acid synthesis and β-oxidation using cellular models of
prostate cancer and normal prostate cells; (2) Determine wh...

## Key facts

- **NIH application ID:** 10073340
- **Project number:** 5R01CA225716-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Shivendra Singh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $480,187
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073340

## Citation

> US National Institutes of Health, RePORTER application 10073340, Biomarkers of Sulforaphane/Broccoli Sprout Extract in Prostate Cancer (5R01CA225716-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10073340. Licensed CC0.

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