Program Official

Principal Investigator

Awardee Organization

University Of South Carolina At Columbia
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Emodin as a chemopreventive agent for breast cancer

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, effective and low-cost chemopreventive agent for breast cancer regardless of the subtype.


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  • Atiya HI, Dvorkin-Gheva A, Hassell J, Patel S, Parker RL, Hartstone-Rose A, Hodge J, Fan D, Ramsdell AF. Intraductal Adaptation of the 4T1 Mouse Model of Breast Cancer Reveals Effects of the Epithelial Microenvironment on Tumor Progression and Metastasis. Anticancer research. 2019 May;39(5):2277-2287. PMID: 31092419
  • Xu Y, Xu Y, Zhu Y, Sun H, Juguilon C, Li F, Fan D, Yin L, Zhang Y. Macrophage miR-34a Is a Key Regulator of Cholesterol Efflux and Atherosclerosis. Molecular therapy : the journal of the American Society of Gene Therapy. 2020 Jan 8;28(1):202-216. Epub 2019 Sep 12. PMID: 31604677
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  • Chaparala A, Tashkandi H, Chumanevich AA, Witalison EE, Windust A, Cui T, Nagarkatti M, Nagarkatti P, Hofseth LJ. Molecules from American Ginseng Suppress Colitis through Nuclear Factor Erythroid-2-Related Factor 2. Nutrients. 2020 Jun 21;12. (6). PMID: 32575883
  • Sun L, Li S, Wang L, Song X. A semiparametric mixture model approach for regression analysis of partly interval-censored data with a cured subgroup. Statistical methods in medical research. 2021 Aug;30(8):1890-1903. Epub 2021 Jul 1. PMID: 34197261
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  • Hodge J, Wang F, Wang J, Liu Q, Saaoud F, Wang Y, Singh UP, Chen H, Luo M, Ai W, Fan D. Overexpression of microRNA-155 enhances the efficacy of dendritic cell vaccine against breast cancer. Oncoimmunology. 2020 Feb 9;9(1):1724761. doi: 10.1080/2162402X.2020.1724761. eCollection 2020. PMID: 32117588
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  • Li Y, Sun W, Saaoud F, Wang Y, Wang Q, Hodge J, Hui Y, Yin S, Lessner SM, Kong X, Fan D. MiR155 modulates vascular calcification by regulating Akt-FOXO3a signalling and apoptosis in vascular smooth muscle cells. Journal of cellular and molecular medicine. 2021 Jan;25(1):535-548. Epub 2020 Nov 18. PMID: 33210462
  • Fang L, Zhao F, Iwanowycz S, Wang J, Yin S, Wang Y, Fan D. Anticancer activity of emodin is associated with downregulation of CD155. International immunopharmacology. 2019 Oct;75:105763. Epub 2019 Jul 17. PMID: 31325728
  • McDonald SJ, VanderVeen BN, Bullard BM, Cardaci TD, Madero SS, Chatzistamou I, Fan D, Murphy EA. Surgical wounding enhances pro-tumor macrophage responses and accelerates tumor growth and lung metastasis in a triple negative breast cancer mouse model. Physiological reports. 2022 Nov;10(21):e15497. PMID: 36325601
  • Sun L, Li S, Wang L, Song X. Variable selection in semiparametric nonmixture cure model with interval-censored failure time data: An application to the prostate cancer screening study. Statistics in medicine. 2019 Jul 20;38(16):3026-3039. Epub 2019 Apr 29. PMID: 31032999
  • Withana Gamage PW, McMahan CS, Wang L. A flexible parametric approach for analyzing arbitrarily censored data that are potentially subject to left truncation under the proportional hazards model. Lifetime data analysis. 2023 Jan;29(1):188-212. Epub 2022 Oct 8. PMID: 36208362
  • Wang J, Wang Q, Guan Y, Sun Y, Wang X, Lively K, Wang Y, Luo M, Kim JA, Murphy EA, Yao Y, Cai G, Fan D. Breast cancer cell-derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and antitumor function. The Journal of clinical investigation. 2022 Oct 3;132. (19). PMID: 35925680
  • Saaoud F, Wang J, Iwanowycz S, Wang Y, Altomare D, Shao Y, Liu J, Blackshear PJ, Lessner SM, Murphy EA, Wang H, Yang X, Fan D. Bone marrow deficiency of mRNA decaying protein Tristetraprolin increases inflammation and mitochondrial ROS but reduces hepatic lipoprotein production in LDLR knockout mice. Redox biology. 2020 Oct;37:101609. Epub 2020 Jun 17. PMID: 32591281
  • Sun L, Li S, Wang L, Song X, Sui X. Simultaneous variable selection in regression analysis of multivariate interval-censored data. Biometrics. 2022 Dec;78(4):1402-1413. Epub 2021 Sep 7. PMID: 34407218
  • Wu W, Wang C, Zang H, Qi L, Azhar M, Nagarkatti M, Nagarkatti P, Cai G, Weiser-Evans MCM, Cui T. Mature Vascular Smooth Muscle Cells, but Not Endothelial Cells, Serve as the Major Cellular Source of Intimal Hyperplasia in Vein Grafts. Arteriosclerosis, thrombosis, and vascular biology. 2020 Aug;40(8):1870-1890. Epub 2020 Jun 4. PMID: 32493169
  • Chaparala A, Poudyal D, Tashkandi H, Witalison EE, Chumanevich AA, Hofseth JL, Nguyen I, Hardy O, Pittman DL, Wyatt MD, Windust A, Murphy EA, Nagarkatti M, Nagarkatti P, Hofseth LJ. Panaxynol, a bioactive component of American ginseng, targets macrophages and suppresses colitis in mice. Oncotarget. 2020 Jun 2;11(22):2026-2036. doi: 10.18632/oncotarget.27592. eCollection 2020 Jun 2. PMID: 32547701
  • McDonald SJ, VanderVeen BN, Velazquez KT, Enos RT, Fairman CM, Cardaci TD, Fan D, Murphy EA. Therapeutic Potential of Emodin for Gastrointestinal Cancers. Integrative cancer therapies. 2022 Jan-Dec;21:15347354211067469. PMID: 34984952
  • Liu Q, Hodge J, Wang J, Wang Y, Wang L, Singh U, Li Y, Yao Y, Wang D, Ai W, Nagarkatti P, Chen H, Xu P, Murphy EA, Fan D. Emodin reduces Breast Cancer Lung Metastasis by suppressing Macrophage-induced Breast Cancer Cell Epithelial-mesenchymal transition and Cancer Stem Cell formation. Theranostics. 2020 Jul 9;10(18):8365-8381. doi: 10.7150/thno.45395. eCollection 2020. PMID: 32724475
  • Zhang X, Sergin I, Evans TD, Jeong SJ, Rodriguez-Velez A, Kapoor D, Chen S, Song E, Holloway KB, Crowley JR, Epelman S, Weihl CC, Diwan A, Fan D, Mittendorfer B, Stitziel NO, Schilling JD, Lodhi IJ, Razani B. High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy. Nature metabolism. 2020 Jan;2(1):110-125. Epub 2020 Jan 23. PMID: 32128508
  • VanderVeen BN, Murphy EA, Carson JA. The Impact of Immune Cells on the Skeletal Muscle Microenvironment During Cancer Cachexia. Frontiers in physiology. 2020 Aug 31;11:1037. doi: 10.3389/fphys.2020.01037. eCollection 2020. PMID: 32982782