期刊
BIOCHEMICAL PHARMACOLOGY
卷 172, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bcp.2019.113752
关键词
13-DCQA; 14-3-3 tau; Breast cancer; Metastasis; Apoptosis
资金
- Tackle Key Problems in Science and Technology Project in Anhui Province, China [1501041177]
- Promoting Project for Team Construction of Anhui Province, China [Z010115006]
- Natural Science Foundation Project of Anhui Province [1908085MC87]
- Scientific Research Foundation of Anhui University [10117700023]
- Academic & Technology Leaders Introduction Project of Anhui University [10117700023]
- 211 Project of Anhui University [10117700023]
14-3-3 tau plays a critical role in tumorigenesis and metastasis of breast cancer and can be used as new drug target protein. Dicaffeoylquinic acids (DCQAs), natural products, have antioxidant, antimicrobial, and anti-inflammatory activities. In this study, the anticancer effects of DCQAs on breast cancer cells MCF-7, MDA-MB-231 cell lines and mechanism in triple negative breast cancer (TNBC) were investigated. First, we screened for DCQAs that could bind to 14-3-3 tau and had a significant inhibitory effect on breast cancer cells. MTT, colony formation, transwell migration, and flow cytometric assays revealed that 1,3-DCQA was the best one of 14-3-3 tau binding protein from DCQAs against breast cancer cell proliferation and metastasis but safe for normal cells. Through molecular docking simulation, overexpression and knockdown assays, we confirmed that 14-3-3 tau was one of 1,3-DCQA target protein. Eukaryotic transcriptome sequencing and western blot analysis demonstrated that 1,3-DCQA binds to 14-3-3 tau to prevent breast cancer proliferation and metastasis via Jak/PI3K/Akt and Raf/ERK pathway, which promote IL6 and CSF3 expression raised by CREB (CREBBP, CREB5) and induced cell apoptosis via Bad/Bax/caspase 9 signaling pathway. Our results provided evidence that 1,3-DCQA can be used as a novel lead compound against breast cancer by inhibition of 14-3-3 protein.
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