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

Autor: Yao Y; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Guo Q; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Cao Y; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Qiu Y; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Tan R; State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, 138 Xinlin Road, Nanjing, 210023, People's Republic of China., Yu Z; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Zhou Y; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., Lu N; State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China. nalu@cpu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2018 Nov 26; Vol. 37 (1), pp. 282. Date of Electronic Publication: 2018 Nov 26.
DOI: 10.1186/s13046-018-0960-7
Abstrakt: Background: Cancer-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.
Methods: In this study, we investigated the in-vitro and in-vivo effects of artemisinin derivatives on inactivating cancer-associated fibroblasts and uncovered its underlying mechanism.
Results: We 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.
Conclusions: Artemisinin derivatives are potential therapeutic agents for the treatment of breast cancer.
Databáze: MEDLINE
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