XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway
Macrophages are the most abundant stromal cells associated with the host immune system in multiple malignancies including breast cancer. With proven clinical efficacy and no noticeable adverse effects, XIAOPI formula (XPS) has been approved for breast hyperplasia treatment by the State Food and Drug...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2019-11-01
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Series: | Frontiers in Pharmacology |
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Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01371/full |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shengqi Wang Shengqi Wang Shengqi Wang Xiaoyan Liu Renlun Huang Renlun Huang Yifeng Zheng Yifeng Zheng Yifeng Zheng Neng Wang Neng Wang Bowen Yang Bowen Yang Honglin Situ Yi Lin Zhiyu Wang Zhiyu Wang Zhiyu Wang Zhiyu Wang |
spellingShingle |
Shengqi Wang Shengqi Wang Shengqi Wang Xiaoyan Liu Renlun Huang Renlun Huang Yifeng Zheng Yifeng Zheng Yifeng Zheng Neng Wang Neng Wang Bowen Yang Bowen Yang Honglin Situ Yi Lin Zhiyu Wang Zhiyu Wang Zhiyu Wang Zhiyu Wang XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway Frontiers in Pharmacology XIAOPI formula tumor-associated macrophages breast cancer stem cells C-X-C motif chemokine ligand 1 M2 phenotype polarization |
author_facet |
Shengqi Wang Shengqi Wang Shengqi Wang Xiaoyan Liu Renlun Huang Renlun Huang Yifeng Zheng Yifeng Zheng Yifeng Zheng Neng Wang Neng Wang Bowen Yang Bowen Yang Honglin Situ Yi Lin Zhiyu Wang Zhiyu Wang Zhiyu Wang Zhiyu Wang |
author_sort |
Shengqi Wang |
title |
XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway |
title_short |
XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway |
title_full |
XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway |
title_fullStr |
XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway |
title_full_unstemmed |
XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 Pathway |
title_sort |
xiaopi formula inhibits breast cancer stem cells via suppressing tumor-associated macrophages/c-x-c motif chemokine ligand 1 pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2019-11-01 |
description |
Macrophages are the most abundant stromal cells associated with the host immune system in multiple malignancies including breast cancer. With proven clinical efficacy and no noticeable adverse effects, XIAOPI formula (XPS) has been approved for breast hyperplasia treatment by the State Food and Drug Administration of China (SFDA) in 2018. The existing knowledge about the anti-breast cancer activities and mechanisms of XPS has been very limited. The present study aimed to investigate whether XPS could exert an anti-breast cancer effect by regulating tumor-associated macrophages (TAMs) in tumor microenvironment. Herein, breast cancer cells and TAMs were co-cultured using the transwell co-culture system to simulate the coexistence of them. XPS could significantly inhibit the proliferation, colony formation, breast cancer stem cells (CSCs) subpopulation, mammosphere formation abilities as well as stemness-related genes expression in both human and mouse breast cancer cells in the co-culture system. Additionally, XPS could suppress M2 phenotype polarization as well as C-X-C motif chemokine ligand 1 (CXCL1) expression and secretion of TAMs. Notably, further mechanistic explorations verified TAMs/CXCL1 as the critical target of XPS in inhibiting breast CSCs self-renewal in the co-culture system as the exogenous CXCL1 administration could abrogate the inhibitory effect of XPS on breast CSCs self-renewal. More importantly, XPS significantly inhibited mammary tumor growth, breast CSCs subpopulation, and TAMs/CXCL1 activity in mouse 4T1-Luc xenografts in vivo without any detectable side effects. Taken together, this study not only uncovers the immunomodulatory mechanism of XPS in treating breast cancer but also sheds novel insights into TAMs/CXCL1 as a potential molecular target for breast CSCs elimination. |
topic |
XIAOPI formula tumor-associated macrophages breast cancer stem cells C-X-C motif chemokine ligand 1 M2 phenotype polarization |
url |
https://www.frontiersin.org/article/10.3389/fphar.2019.01371/full |
work_keys_str_mv |
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doaj-78075ee34c48406dab24dc2b5c77bd452020-11-24T21:18:38ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-11-011010.3389/fphar.2019.01371484719XIAOPI Formula Inhibits Breast Cancer Stem Cells via Suppressing Tumor-Associated Macrophages/C-X-C Motif Chemokine Ligand 1 PathwayShengqi Wang0Shengqi Wang1Shengqi Wang2Xiaoyan Liu3Renlun Huang4Renlun Huang5Yifeng Zheng6Yifeng Zheng7Yifeng Zheng8Neng Wang9Neng Wang10Bowen Yang11Bowen Yang12Honglin Situ13Yi Lin14Zhiyu Wang15Zhiyu Wang16Zhiyu Wang17Zhiyu Wang18Integrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaPost-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaPost-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaCollege of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaIntegrative Research Laboratory of Breast Cancer, The Research Center for Integrative Medicine, Discipline of Integrated Chinese and Western Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, ChinaPost-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, ChinaCollege of Basic Medicine, Guangzhou University of Chinese Medicine, Guangzhou, ChinaMacrophages are the most abundant stromal cells associated with the host immune system in multiple malignancies including breast cancer. With proven clinical efficacy and no noticeable adverse effects, XIAOPI formula (XPS) has been approved for breast hyperplasia treatment by the State Food and Drug Administration of China (SFDA) in 2018. The existing knowledge about the anti-breast cancer activities and mechanisms of XPS has been very limited. The present study aimed to investigate whether XPS could exert an anti-breast cancer effect by regulating tumor-associated macrophages (TAMs) in tumor microenvironment. Herein, breast cancer cells and TAMs were co-cultured using the transwell co-culture system to simulate the coexistence of them. XPS could significantly inhibit the proliferation, colony formation, breast cancer stem cells (CSCs) subpopulation, mammosphere formation abilities as well as stemness-related genes expression in both human and mouse breast cancer cells in the co-culture system. Additionally, XPS could suppress M2 phenotype polarization as well as C-X-C motif chemokine ligand 1 (CXCL1) expression and secretion of TAMs. Notably, further mechanistic explorations verified TAMs/CXCL1 as the critical target of XPS in inhibiting breast CSCs self-renewal in the co-culture system as the exogenous CXCL1 administration could abrogate the inhibitory effect of XPS on breast CSCs self-renewal. More importantly, XPS significantly inhibited mammary tumor growth, breast CSCs subpopulation, and TAMs/CXCL1 activity in mouse 4T1-Luc xenografts in vivo without any detectable side effects. Taken together, this study not only uncovers the immunomodulatory mechanism of XPS in treating breast cancer but also sheds novel insights into TAMs/CXCL1 as a potential molecular target for breast CSCs elimination.https://www.frontiersin.org/article/10.3389/fphar.2019.01371/fullXIAOPI formulatumor-associated macrophagesbreast cancer stem cellsC-X-C motif chemokine ligand 1M2 phenotype polarization |