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 Q 0 (CoQ 0 ), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial–mesenchymal transition (EMT) and antimetastatic attributes of CoQ 0 in TNBC (MDA-MB-231). Methods Invasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with β-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 CoQ 0 (0.5–2 μM) 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, CoQ 0 inhibited metastasis and EMT in TGF-β/TNF-α-stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase–injected live mice demonstrated that CoQ 0 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 β-catenin with siRNA stimulated CoQ 0 -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, β-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed. Conclusions CoQ 0 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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1196-x) contains supplementary material, which is available to authorized users.

LTBP1 promotes esophageal squamous cell carcinoma progression through epithelial-mesenchymal transition and cancer-associated fibroblasts transformation

“…The results were consistent with previous reports that esophageal cancers cells with EMT growth pattern exhibited more resistance to chemotherapeutic drugs [34,35]. It has been reported that Anti-EMT properties could promoted apoptosis [36]. As the critical regulators of apoptosis, BCL-2 family proteins are also correlated with chemoresistance [37,38].…”

Indoxyl sulfate‐induced calcification of vascular smooth muscle cells via the PI3K/Akt/NF‐κB signaling pathway

“…These data indicated that treatment of HASMCs with IS induced the activated of PI3K/Akt signaling pathway. As NF‐κB is a transcription factor and its activation could be in part regulated by the upstream pathway of PI3K/Akt (Yang et al, ), we measured the phosphorylation of NF‐κB p65 protein level under the presence of LY294002 stimulation with IS. As shown in Figure c, IS significantly activated the phosphorylation of NF‐κB p65, whereas the presence of LY294002 reversed the activated effect of IS on the phosphorylation of NF‐κB p65.…”

EMT related circular RNA expression profiles identify circSCYL2 as a novel molecule in breast tumor metastasis

“…4A. Although differentially expressed circRNAs have been proposed to be closely associated with EMT (12,15), the roles of circRNAs in breast cancer EMT remain unclear. The present study aimed to identify novel circRNAs that regulate EMT of breast cancer cells.…”

“…cORM-A1 and dETA/NO combination therapy showed antimetastatic action and resulted in normalization of endothelial metabolism, diminution of platelet activation, and inhibition of EMT progression (12). coenzyme Q 0 attributed to the phosphatidyl inositol 3 kinase (PI3K)/protein kinase B (AKT)/nuclear factor (NF)κB/matrix metalloproteinase-9 signaling pathway through reactive oxygen species-mediated apoptosis can inhibit the progression of metastasis as well as EMT (in vitro and in vivo) (15). Metastasis of breast cancer remains challenging for the current clinical treatments and more than half of the patients suffer from a disease relapse due to distant metastases (16).…”