Anti-EMT properties of CoQ0 attributed to PI3K/AKT/NFKB/MMP-9 signaling pathway through ROS-mediated apoptosis.

ABSTRACT: BACKGROUND:Breast cancer is the most prevalent cancer among women. In triple-negative breast cancer (TNBC) cells, a novel quinone derivative, coenzyme Q0 (CoQ0), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial-mesenchymal transition (EMT) and antimetastatic attributes of CoQ0 in TNBC (MDA-MB-231). METHODS:Invasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with ?-catenin siRNA. Through Western blotting and RT-PCR, the major signaling pathways' protein expressions were examined, and the biopsied tumor tissues underwent immunohistochemical and hematoxylin and eosin staining as well as Western blotting. RESULTS:CoQ0 (0.5-2??M) hindered tumor migration, invasion, and progression. Additionally, it caused MMP-2/-?9, uPA, uPAR, and VEGF downregulation. Furthermore, in highly metastatic MDA-MB-231 cells, TIMP-1/2 expression was subsequently upregulated and MMP-9 expression was downregulated. In addition, CoQ0 inhibited metastasis and EMT in TGF-?/TNF-?-stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase-injected live mice demonstrated that CoQ0 significantly inhibited metastasis of the breast cancer to the lungs and inhibited the development of tumors in MDA-MB-231 xenografted nude mice. Silencing of ?-catenin with siRNA stimulated CoQ0-inhibited EMT. Western blotting as well as histological analysis established that CoQ0 reduced xenografted tumor development because apoptosis induction, cell-cycle inhibition, E-cadherin upregulation, ?-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed. CONCLUSIONS:CoQ0 inhibited the progression of metastasis as well as EMT (in vitro and in vivo). The described approach has potential in treating human breast cancer metastasis.

SUBMITTER: Yang HL 

PROVIDER: S-EPMC6505074 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature