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Isoliquiritigenin Inhibits Triple-Negative Breast Cancer Progression via Targeting the IRF5/SLC7A5/IDO1-Mediated
Sihai Duan1,2, Xiaoyan Li3, Cailu Song3
1Department of Breast and Thyroid Surgery, The Central Hospital of Yongzhou, Yongzhou, 425007, China.
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.
Insights
Isoliquiritigenin (ISL) suppresses triple-negative breast cancer (TNBC) by targeting interferon regulatory factor 5 (IRF5). This natural compound disrupts tryptophan metabolism, offering a potential new therapeutic strategy for TNBC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) presents a poor prognosis.
- Isoliquiritigenin (ISL), a chalcone from licorice, is investigated for its therapeutic potential.
- Interferon regulatory factor 5 (IRF5) is a key factor in TNBC.
Purpose of the Study:
- To elucidate the molecular mechanisms of ISL targeting IRF5 in TNBC.
- To determine the role of IRF5 in TNBC cell proliferation and metabolism.
- To evaluate ISL's impact on tryptophan metabolism pathways in TNBC.
Main Methods:
- IRF5 knockdown in TNBC cell lines using short hairpin RNA.
- Cell proliferation assessed via CCK-8 and colony formation assays.
- Expression analysis of IRF5, SLC7A5, and IDO1 using Western blotting and RT-PCR.
- Quantification of intracellular tryptophan and metabolites via HPLC.
Main Results:
- IRF5 is highly expressed in TNBC cell lines and its silencing inhibits proliferation.
- IRF5 knockdown reduces SLC7A5 and IDO1 expression, decreasing intracellular tryptophan.
- ISL treatment suppressed TNBC cell proliferation and disrupted tryptophan metabolism.
Conclusions:
- ISL inhibits TNBC progression by downregulating IRF5.
- ISL interferes with SLC7A5/IDO1-mediated tryptophan metabolic reprogramming.
- ISL represents a potential therapeutic agent for TNBC.
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