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Artemisinin derivatives inactivate cancer-associated fibroblasts through suppressing TGF-β signaling in breast cancer

Authors
  • Yao, Yuyuan1
  • Guo, Qinglong1
  • Cao, Yue1
  • Qiu, Yangmin1
  • Tan, Renxiang2
  • Yu, Zhou1
  • Zhou, Yuxin1
  • Lu, Na1
  • 1 China Pharmaceutical University, State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, 24 Tongjiaxiang, Nanjing, 210009, People’s Republic of China , Nanjing (China)
  • 2 Nanjing University of Chinese Medicine, State Key Laboratory Cultivation Base for TCM Quality and Efficacy, 138 Xinlin Road, Nanjing, 210023, People’s Republic of China , Nanjing (China)
Type
Published Article
Journal
Journal of Experimental & Clinical Cancer Research
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 26, 2018
Volume
37
Issue
1
Identifiers
DOI: 10.1186/s13046-018-0960-7
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundCancer-associated fibroblasts (CAFs) are activated fibroblasts associated with cancer. They have an important role in tumor growth and metastasis. Artemisinin (ART) is a sesquiterpene lactone extracted from Chinese herb qinghao, and artemether (ARM), artesunate (ARS) and dihydroartemisinin (DHA) were synthesized derivatives of artemisinin, which also have anti-malarial and anti-cancer effects such as artemisinin.MethodsIn this study, we investigated the in-vitro and in-vivo effects of artemisinin derivatives on inactivating cancer-associated fibroblasts and uncovered its underlying mechanism.ResultsWe demonstrated that ARS and DHA could revert L-929-CAFs and CAFs from activated to inactivated state in vitro. Mechanically, ARS and DHA could suppress TGF-β signaling to inhibit activation of L-929-CAFs and CAFs, and decreased interaction between tumor and tumor microenvironment. The results showed that ARS and DHA could suppress CAFs-induced breast cancer growth and metastasis in the orthotopic model. Conformably, ARS and DHA suppressed TGF-β signaling to inactivate cancer-associated fibroblasts and inhibit cancer metastasis in vivo.ConclusionsArtemisinin derivatives are potential therapeutic agents for the treatment of breast cancer.

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