Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling.

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.

• Authors: Hui Shi, Luping Zhao, Xinlin Guo, Runping Fang, Hui Zhang, Guanjun Dong, Jia Fu, Fenglian Yan, Junfeng Zhang, Zhaochen Ning, Qun Ma, Zhihua Li, Chunxia Li, Jun Dai, Chuanping Si, Huabao Xiong
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 17 (Sep 02 2020) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 32887217 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CTNNB1 protein, human
• Cytokines
• Furans
• Lignans
• STAT3 Transcription Factor
• STAT3 protein, human
• TSLP protein, human
• beta Catenin
• Granulocyte-Macrophage Colony-Stimulating Factor
• arctigenin

Topics

• Animals
• Apoptosis
• Biomarkers, Tumor
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Movement
• Cell Proliferation
• Cytokines (genetics, metabolism)
• Female
• Furans (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics, metabolism)
• Humans
• Lignans (pharmacology)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• STAT3 Transcription Factor (genetics, metabolism)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays
• beta Catenin (genetics, metabolism)