# Targeting cancer stem-like cells and inflammation for colon cancer chemoprevention

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $173,208

## Abstract

PROJECT SUMMARY/ABSTRACT
A hallmark of colorectal cancers is the loss of the adenomatous polyposis coli (APC) tumor suppressor gene,
resulting in dysregulated Wnt signaling and the oncogenic transformation of colon stem cells into cancer stem
cells. In addition, inflammation, a major risk factor for the development of colorectal cancer, can upregulate
cytokines that can drive the formation of tumor-initiating cells. Thus, strategies that target both inflammation and
cancer stem cells may be effective in decreasing the risk of developing colorectal cancer. Sulforaphane, a
naturally-occurring isothiocyanate derived from cruciferous vegetables and particularly abundant in broccoli, has
well-established anti-inflammatory and anti-tumor activities. However, the precise mechanism by which it inhibits
tumorigenesis and whether it is capable of reducing colorectal cancer risk remain to be determined. We have
previously demonstrated that sulforaphane inhibits NFκB-mediated inflammatory responses in breast cancer
cells as well as the proliferation and self-renewal capacity of breast cancer stem cells. We now have preliminary
data strongly suggesting that sulforaphane has similar effects in colon cancer cells and more importantly, can
inhibit the growth of human organoids driven by an APC mutation. Furthermore, mice fed a preparation of broccoli
that is enriched in sulforaphane are more resistant to the development of colonic inflammation and adenoma
formation. In this proposal, we will examine the efficacy of a pharmaceutical preparation of sulforaphane in
suppressing the establishment of tumor-initiating cells driven by dysregulated Wnt signaling and determine its
ability to inhibit colon stem cells capable of malignant transformation using in vivo mouse models and in vitro
patient-derived organoid cultures. The proposed studies will be critical in developing a synthetic analog of
sulforaphane as a chemopreventive agent in patients at high risk for developing colorectal cancer.

## Key facts

- **NIH application ID:** 10817254
- **Project number:** 5R21CA273646-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** GRACE Y. CHEN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $173,208
- **Award type:** 5
- **Project period:** 2023-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10817254

## Citation

> US National Institutes of Health, RePORTER application 10817254, Targeting cancer stem-like cells and inflammation for colon cancer chemoprevention (5R21CA273646-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10817254. Licensed CC0.

---

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