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  • Title: Dihydroartemisinin inhibits the tumorigenesis and metastasis of breast cancer via downregulating CIZ1 expression associated with TGF-β1 signaling.
    Author: Li Y, Zhou X, Liu J, Gao N, Yang R, Wang Q, Ji J, Ma L, He Q.
    Journal: Life Sci; 2020 May 01; 248():117454. PubMed ID: 32088211.
    Abstract:
    AIMS: Dihydroartemisinin (DHA) is currently considered as the promising cancer therapeutic drug. In this study, we aimed to investigate the anti-proliferative and anti-metastasis effects of DHA. MAIN METHODS: Utilizing breast cancer cells MCF-7, MDA-MB-231 and BT549, cell proliferation, migration and invasion were detected. RT-qPCR was performed to detect CIZ1, TGF-β1 and Snail expression, and the interactions of these related molecules were analyzed by GeneMANIA database. Western blot detected CIZ1, TGF-β1/Smads signaling and Snail expression in DHA-treated cells, in TGFβ1-induced cells with enhanced metastatic capacity, and in cells treated with DHA plus TGFβ1/TGFβ1 inhibitor SD-208. KEY FINDINGS: Results indicated DHA inhibited breast cancer cell proliferation and migration, with more potent effects compared with that of artemisinin. RT-qPCR and Western blot showed DHA inhibited CIZ1, TGF-β1 and Snail expression, and these molecules were shown to have protein-protein interactions by bioinformatics. Furthermore, TGFβ1-treatment enhanced MCF-7 migration and invasion, and CIZ1, TGF-β1/Smads signaling and snail activities; DHA, SD-208, combination of DHA and SD-208 reversed these conditions, preliminarily proving the cascade regulation between TGF-β1 signaling and CIZ1. MCF-7 xenografts model demonstrated the inhibition of DHA on tumor burden, and its mechanisms and well-tolerance in vivo; combination of DHA and SD-208 tried by us for the first time showed better treatment effects, but possible liver impairment made its use still keep cautious. SIGNIFICANCE: DHA treatment inhibits the proliferation and metastasis of breast cancer, through suppressing TGF-β1/Smad signaling and CIZ1, suggesting the promising potential of DHA as a well-tolerated antitumor TGF-β1 pathway inhibitor.
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