# Emodin as a chemopreventive agent for breast cancer

> **NIH NIH R01** · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · 2022 · $324,810

## Abstract

Summary: Breast cancer is the most prevalent cancer and the second leading cause of cancer-related death
in women in the United States. However, little progress has been made in preventing the incidence of breast
cancer. Most breast cancer mortality results from metastatic recurrence after initial success of surgery and/or
other therapies. Although extended treatment with selective estrogen receptor modulators and aromatase
inhibitors have been proven effective in preventing metastatic recurrence of breast cancer, the benefit is limited
to ER+ breast cancer, and severe adverse effects make them suboptimal for long-term use. Currently there are
no preventive agents for ER- breast cancer. This is of particular relevance given the high metastatic recurrence
rate and the resulting poor prognosis of triple negative breast cancer. One common feature of breast cancer,
regardless of the subtypes, is the pro-tumor nature of the tumor microenvironment, which contains abundant
MΦs, called tumor-associated macrophages (TAMs). TAMs promote tumor development and metastasis
through inducing immunosuppression, promoting angiogenesis, enhancing tumor cell proliferation and
invasiveness, and facilitating cancer stem cell (CSC) formation and maintenance. Due to their determinant
roles in all stages of cancer development, TAMs have been considered as a therapeutic target for cancer.
However, MΦs have not yet been exploited as a target for breast cancer prevention. Emodin is a small
molecule compound derived from many plants including several Chinese herbs. Our published studies showed
that emodin inhibited breast cancer growth and metastasis in orthotopic mouse models through reducing MΦ
recruitment to tumors and lungs and suppressing their M2-like polarization by acting on both MΦs and breast
cancer cells. Our preliminary studies further showed that emodin could suppress TGFβ1-induced epithelial to
mesenchymal transition and diminish the stemness of breast cancer cells, and reduce the death due to
metastatic recurrence after surgical removal of primary tumors in an orthotopic breast cancer model.
Importantly, a comprehensive NIH toxicology study showed that emodin is very safe for long-term use in mice
and rats. Given the important roles of MΦs in breast cancer initiation and metastatic recurrence, and based on
our published and preliminary data, we hypothesize that emodin can be developed as a safe and effective
chemopreventive agent for breast cancer incidence and metastatic recurrence by virtue of its ability to block
the tumor-promoting crosstalk between cancer cells and MΦs. Two specific aims are proposed: SA1. To
determine the effects of emodin on preventing breast cancer onset and post-surgery metastatic recurrence in
mouse models; and SA2. To elucidate the mechanisms by which emodin prevents breast cancer onset and
metastatic recurrence. The success of the proposed preclinical studies will set a stage for clinical trials to
develop emodin as a new safe, eff...

## Key facts

- **NIH application ID:** 10378552
- **Project number:** 5R01CA218578-05
- **Recipient organization:** UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
- **Principal Investigator:** Daping Fan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $324,810
- **Award type:** 5
- **Project period:** 2018-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10378552

## Citation

> US National Institutes of Health, RePORTER application 10378552, Emodin as a chemopreventive agent for breast cancer (5R01CA218578-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10378552. Licensed CC0.

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