1,3-Dicaffeoylquinic acid targeting 14-3-3 tau suppresses human breast cancer cell proliferation and metastasis through IL6/JAK2/PI3K pathway

  • Biochem Pharmacol. 2020 Feb;172:113752. doi: 10.1016/j.bcp.2019.113752.
Yuhang Zhou  1 ,  Xiang Fu  1 ,  Yanqing Guan  2 ,  Mengting Gong  1 ,  Kan He  3 ,  Bei Huang  4
Affiliations
  • 1. School of Life Sciences, Anhui University, Hefei 230601, China; Center for Stem Cell and Translational Medicine, Anhui University, Hefei 230601, China.
  • 2. School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
  • 3. School of Life Sciences, Anhui University, Hefei 230601, China; Center for Stem Cell and Translational Medicine, Anhui University, Hefei 230601, China. Electronic address: [email protected].
  • 4. School of Life Sciences, Anhui University, Hefei 230601, China; Center for Stem Cell and Translational Medicine, Anhui University, Hefei 230601, China. Electronic address: [email protected].
PMID: 31836387 DOI: 10.1016/j.bcp.2019.113752
Abstract

14-3-3τ 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 14-3-3τ 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 14-3-3τ 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 14-3-3τ was one of 1,3-DCQA target protein. Eukaryotic transcriptome Sequencing and western blot analysis demonstrated that 1,3-DCQA binds to 14-3-3τ 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.

Keywords
13-DCQA; 14-3-3τ; Apoptosis; Breast cancer; Metastasis.
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