Thymoquinone suppresses invasion and metastasis in bladder cancer cells by reversing EMT through the Wnt/β-catenin signaling pathway. (1st April 2020)

• Record Type: Journal Article
• Authors: Zhang, Mengzhao; Du, Hongxia; Wang, Lu; Yue, Yangyang; Zhang, Pu; Huang, Zhixin; Lv, Wei; Ma, Jianbin; Shao, Qiuya; Ma, Minghai; Liang, Xiao; Yang, Tao; Wang, Weiyi; Zeng, Jin; Chen, Guanqiu; Wang, Xinyang; Fan, Jinhai
• Is Part Of: Chemico-biological interactions. Volume 320(2020)
• Publication Date: 2020-04-01
• Subjects: Thymoquinone -- Bladder cancer -- EMT -- Wnt/β-catenin signaling pathway -- Metastasis; TQ thymoquinone -- EMT epithelial-mesenchymal transition -- TGF-β transforming growth factor-β -- MTT 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide -- APC adenomatous polyposis -- HE hematoxylin -- TCF/LEF-1 T-cell factor 1/lymphoid-enhancer factor-1 -- IF immunofluorescence -- IHC immunohistochemistry -- i.p intraperitoneal; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2020.109022
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer, which makes bladder cancer difficult to cure. Bladder cancer is the most common malignancy of the urinary system, and distant metastasis is the leading cause of death. Therefore, finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future. Thymoquinone (TQ), the major active compound isolated from black seed oil ( Nigella sativa ), has been reported to exhibit anti-inflammatory and anticancer abilities. TQ can exhibit its antitumor effect by inhibiting the proliferation and metastasis of cancer cells. However, the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood. First, in this research, we demonstrate that TQ can reverse EMT by upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin and vimentin. Furthermore, we demonstrate that TQ can suppress the activation of the Wnt/β-catenin signaling pathway and inhibit the expression of β-catenin target genes, such as MYC, Axin-2, MMP7, CyclinD1 and MET, which play crucial roles in EMT and cancer progression. Additionally, we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung. Taken together, our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer. Highlights: Thymoquinone inhibits migration and invasion in bladder cancer cells. Thymoquinone suppresses EMT in bladder cancer cells. Thymoquinone inhibits the activation of Wnt/β-catenin signaling pathway. β-catenin plays a key role in EMT inhibition induced by TQ. Thymoquinone exerts an anti-metastasis effect of bladder cancer in vivo.