Open Access

ARTICLE

Isoliquiritigenin Inhibits Triple-Negative Breast Cancer Progression via Targeting the IRF5/SLC7A5/IDO1-Mediated Tryptophan Metabolism Pathway

Sihai Duan^1,2,#, Xiaoyan Li^3,#, Cailu Song³, Song Wu³, Yunyun Tang^3,4, Qing Bao^3,4, Na Li^3,*, Hailin Tang^3,*

1 Department of Breast and Thyroid Surgery, The Central Hospital of Yongzhou, Yongzhou, 425007, China
2 Department of Breast and Thyroid Surgery, Yongzhou Hospital Affiliated to University of South China, Yongzhou, 425007, China
3 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China
4 Department of Basic Medicine, School of Health and Wellness Sciences, Guangzhou Kangda Vocational Technical College, Guangzhou, 510555, China

* Corresponding Authors: Na Li. Email: ; Hailin Tang. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Breast Cancer Biomarkers and Drug Targets Discoveries Towards a More Personalized Treatment Setting)

Oncology Research 2025, 33(11), 3543-3556. https://doi.org/10.32604/or.2025.068292

Received 25 May 2025; Accepted 12 August 2025; Issue published 22 October 2025

Abstract

Objectives: Triple-negative breast cancer (TNBC) is the breast cancer subtype with the poorest prognosis. This study aimed to elucidate the molecular pathways through which isoliquiritigenin (ISL), a natural chalcone compound derived from licorice and other plant roots, targets interferon regulatory factor 5 (IRF5) in TNBC. Methods: TNBC cell lines were cultured and subjected to IRF5 knockdown using short hairpin RNA. Cell proliferation was assessed by cell counting kit-8 (CCK-8) assay and colony formation assays. Western blotting and quantitative reverse transcription polymerase chain reaction (RT-PCR) were employed to measure expression levels of IRF5, solute carrier family 7 member 5 (SLC7A5), and indoleamine 2,3-dioxygenase 1 (IDO1). Intracellular tryptophan and its metabolites were quantified using commercially available assay kits and high-performance liquid chromatography (HPLC). TNBC cells were treated with various concentrations of ISL to evaluate its effects on proliferation and tryptophan metabolism. Results: IRF5 was highly expressed in TNBC cell lines. Silencing IRF5 significantly inhibited cellular proliferation and growth. Knockdown of IRF5 reduced the expression of SLC7A5 and IDO1, leading to decreased intracellular levels of tryptophan and its metabolites. ISL markedly suppressed TNBC cell proliferation and disrupted tryptophan metabolism in tumor cells. Conclusion: ISL may inhibit TNBC progression by downregulating IRF5 and interfering with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming, suggesting a potential therapeutic mechanism for TNBC treatment.

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