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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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