Artemisinin derivatives inactivate cancer-associated fibroblasts through suppressing TGF-ß signaling in breast cancer.
J Exp Clin Cancer Res
; 37(1): 282, 2018 Nov 26.
Article
en En
| MEDLINE
| ID: mdl-30477536
ABSTRACT
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-ß 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-ß 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Mama
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Factor de Crecimiento Transformador beta
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Artemisininas
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Fibroblastos Asociados al Cáncer
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Antimaláricos
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Exp Clin Cancer Res
Año:
2018
Tipo del documento:
Article