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Published on: October 27, 2020
Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling
Hui Shi1, Luping Zhao2, Xinlin Guo2
1Institute of Immunology and Molecular Medicine, Jining Medical University, Jining 272067, China.
Abstract:
Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from Arctium lappa L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.
Insights
Arctigenin, a compound from Arctium lappa L., inhibits breast cancer progression by reducing tumor-promoting cytokines like GM-CSF and TSLP. This natural compound targets key signaling pathways, offering a promising avenue for cytokine-targeted breast cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Invasive breast cancer progression is influenced by cytokines within the tumor microenvironment.
- Targeting these cytokines presents a promising therapeutic strategy for breast cancer treatment.
Purpose of the Study:
- To investigate the effects of arctigenin, a natural compound, on tumor-promoting cytokines in breast cancer.
- To elucidate the underlying mechanisms by which arctigenin impacts breast cancer cell proliferation, invasion, and stemness.
Main Methods:
- Assessed the impact of arctigenin on cytokine levels (GM-CSF, MMP-3, MMP-9, TSLP) in breast cancer cells.
- Evaluated arctigenin's effects on cell proliferation, invasion, and stemness in vitro and in vivo.
- Investigated the molecular mechanisms involving NF-κB p65, STAT3, and β-catenin signaling pathways.
Main Results:
- Arctigenin decreased tumor-promoting cytokines GM-CSF and TSLP, inhibiting breast cancer cell proliferation, invasion, and stemness.
- Mechanistically, arctigenin reduced GM-CSF and TSLP promoter activity by inhibiting NF-κB p65 nuclear translocation.
- Arctigenin-mediated cytokine depletion suppressed STAT3 phosphorylation and β-catenin signaling.
Conclusions:
- Arctigenin demonstrates potential as a therapeutic agent by targeting tumor-promoting cytokines in breast cancer.
- The findings offer new insights into cytokine-driven breast cancer progression and highlight arctigenin's role in modulating these pathways.
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