# Identification of Natural Compound Combinations for Prevention of Prostate Cancer

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2020 · $501,955

## Abstract

PROJECT SUMMARY
The overall goal of the proposed research is to develop novel strategies, using combinations of phytochemicals
for the prevention of prostate cancer (PCa). In the United States, PCa is the most frequently diagnosed non-
cutaneous cancer and the second leading cause of cancer-related mortality in men with an estimated 164,690
new cases and an estimated 29,430 deaths in 2018 (American Cancer Society). We have recently found that
several combinations of natural compounds together with ursolic acid (UA) [i.e., UA + curcumin (CURC) and
UA + resveratrol (RES)] are highly effective at depleting cellular ATP levels and at inhibiting the growth/survival
of both mouse (HMVP2, a PCa cell line derived from HiMyc mice) and human (DU145, C4-2B) PCa cell lines.
Both of these combinations produced a synergistic inhibition of PCa cell growth in vitro and also synergistically
inhibited the growth of HMVP2 cells in an allograft tumor model when administered in the diet. Furthermore,
metabolomics analyses of PCa tumor cells indicate that the effective phytochemical combinations reduced
glutamine uptake which likely contributed to the enhanced tumor growth inhibitory activity observed. We have
recently obtained additional synergistic combinations using a two-tiered screen with enoxolone (ENO) as the
lead compound involving ATP depletion and inhibition of glutamine uptake. One of these combinations (ENO +
silibinin) was further tested and shown to synergistically inhibit growth of HMVP2 PCa cells in vivo as further
proof of principle for this approach. In this proposal, we will test the hypothesis that combinations of
certain natural compounds that can be identified by their ability to deplete cellular ATP and block
glutamine uptake will be highly effective, synergistic chemopreventive agents for PCa. We will also test
the hypothesis that effective combinations will have the ability to inhibit specific oncogenic
metabolism and signaling pathways important for PCa development and progression. The Specific Aims
are: 1: Evaluate combinations of natural compounds for their ability to synergistically and selectively inhibit
growth properties of PCa cell lines; 2: Examine the most effective combinations of agents identified in Specific
Aim 1 for their effects on oncogenic signaling pathways (e.g., Stat3, Src, NFκB, AMPK, mTOR and
CXCL12/CXCR4) as well as metabolic pathway changes (e.g., glutamine uptake and utilization, lipid profiles,
etc); 3: Examine the effects of selected natural compound combinations for their ability to prevent PCa
development/progression in two relevant mouse models of PCa (HiMyc and PTENpcko); and 4: Continue
screening larger libraries of natural compounds to identify novel top-hit compounds and screen compound
combinations for their ability to synergistically deplete cellular ATP levels and block glutamine uptake in PCa
cell lines. Completion of the proposed studies will lead to novel approaches for identifying combinations of
phyto...

## Key facts

- **NIH application ID:** 9856419
- **Project number:** 5R01CA228404-02
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** John DiGiovanni
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,955
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9856419

## Citation

> US National Institutes of Health, RePORTER application 9856419, Identification of Natural Compound Combinations for Prevention of Prostate Cancer (5R01CA228404-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9856419. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*