Abstract
BackgroundBreast 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).MethodsInvasion, 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.ResultsCoQ0 (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, CoQ0 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 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 β-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, β-catenin downregulation, and metastasis and EMT regulatory protein modulation were observed.ConclusionsCoQ0 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.
Highlights
Breast cancer is the most prevalent cancer among women
These results indicated that coenzyme Q0 (CoQ0) was more potent against triple-negative breast cancer (TNBC) than against non-tumorigenic cells (Fig. 1b)
The results suggest that Matrix metalloproteases (MMPs)-9, which is a crucial factor for metastasis, was inhibited by CoQ0 treatment
Summary
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. Breast cancer is the commonest cancer to affect women, and in Taiwanese women, it is the leading cause of deaths from cancer [1] It possesses highly metastatic and invasive properties, which explain its high mortality rate [2]. In cancer cells, polarized epithelial cells complete multifaceted changes that cause them to begin expressing a mesenchymal phenotype and undergo migration, invasion, and metastasis. This process is referred to as the epithelial–mesenchymal transition (EMT) [6]. EMT involves AKT/GSK or NFκB-mediated expression of Snail and promotes cell invasion and migration in various cancers, such as breast, renal, and colon cancers [10, 11]. Few studies have investigated the suppression of molecular events and EMT responsible for EMT inhibition in anticancer treatment
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