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

Autor: Yang HL; Institute of Nutrition, College of Biopharmaceuticals and Food Sciences, China Medical University, Taichung, 40402, Taiwan., Thiyagarajan V; Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan., Shen PC; Institute of Nutrition, College of Biopharmaceuticals and Food Sciences, China Medical University, Taichung, 40402, Taiwan., Mathew DC; Institute of Nutrition, College of Biopharmaceuticals and Food Sciences, China Medical University, Taichung, 40402, Taiwan., Lin KY; Department of Medical Research, Chi-Mei Medical Center, Tainan, 710, Taiwan., Liao JW; Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, 40227, Taiwan., Hseu YC; Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, No. 91, Hsueh-Shih Road, Taichung, 40402, Taiwan. ychseu@mail.cmu.edu.tw.; Department of Health and Nutrition Biotechnology, Asia University, Taichung, 41354, Taiwan. ychseu@mail.cmu.edu.tw.; Chinese Medicine Research Center, China Medical University, Taichung, 40402, Taiwan. ychseu@mail.cmu.edu.tw.; Research Center of Chinese Herbal Medicine, China Medical University, Taichung, 40402, Taiwan. ychseu@mail.cmu.edu.tw.
Jazyk: angličtina
Zdroj: Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2019 May 08; Vol. 38 (1), pp. 186. Date of Electronic Publication: 2019 May 08.
DOI: 10.1186/s13046-019-1196-x
Abstrakt: 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.
Databáze: MEDLINE
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