Cargando…
Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling
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 decreas...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503539/ https://www.ncbi.nlm.nih.gov/pubmed/32887217 http://dx.doi.org/10.3390/ijms21176357 |
_version_ | 1783584417301659648 |
---|---|
author | Shi, Hui Zhao, Luping Guo, Xinlin Fang, Runping Zhang, Hui Dong, Guanjun Fu, Jia Yan, Fenglian Zhang, Junfeng Ning, Zhaochen Ma, Qun Li, Zhihua Li, Chunxia Dai, Jun Si, Chuanping Xiong, Huabao |
author_facet | Shi, Hui Zhao, Luping Guo, Xinlin Fang, Runping Zhang, Hui Dong, Guanjun Fu, Jia Yan, Fenglian Zhang, Junfeng Ning, Zhaochen Ma, Qun Li, Zhihua Li, Chunxia Dai, Jun Si, Chuanping Xiong, Huabao |
author_sort | Shi, Hui |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7503539 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75035392020-09-23 Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling Shi, Hui Zhao, Luping Guo, Xinlin Fang, Runping Zhang, Hui Dong, Guanjun Fu, Jia Yan, Fenglian Zhang, Junfeng Ning, Zhaochen Ma, Qun Li, Zhihua Li, Chunxia Dai, Jun Si, Chuanping Xiong, Huabao Int J Mol Sci Article 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. MDPI 2020-09-02 /pmc/articles/PMC7503539/ /pubmed/32887217 http://dx.doi.org/10.3390/ijms21176357 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Shi, Hui Zhao, Luping Guo, Xinlin Fang, Runping Zhang, Hui Dong, Guanjun Fu, Jia Yan, Fenglian Zhang, Junfeng Ning, Zhaochen Ma, Qun Li, Zhihua Li, Chunxia Dai, Jun Si, Chuanping Xiong, Huabao Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title | Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title_full | Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title_fullStr | Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title_full_unstemmed | Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title_short | Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling |
title_sort | arctigenin attenuates breast cancer progression through decreasing gm-csf/tslp/stat3/β-catenin signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503539/ https://www.ncbi.nlm.nih.gov/pubmed/32887217 http://dx.doi.org/10.3390/ijms21176357 |
work_keys_str_mv | AT shihui arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT zhaoluping arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT guoxinlin arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT fangrunping arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT zhanghui arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT dongguanjun arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT fujia arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT yanfenglian arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT zhangjunfeng arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT ningzhaochen arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT maqun arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT lizhihua arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT lichunxia arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT daijun arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT sichuanping arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling AT xionghuabao arctigeninattenuatesbreastcancerprogressionthroughdecreasinggmcsftslpstat3bcateninsignaling |