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Juglone suppresses epithelialmesenchymal transition in prostate cancer cells via the protein kinase B/glycogen synthase kinase3β/Snail signaling pathway

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Epithelialmesenchymal transition (EMT) serves an important role in the metastasis of prostate cancer. Juglone is a natural compound isolated from plants that is reported to possess potent cytotoxic properties. However, there are no studies on the antiEMT effect of juglone in prostate cancer, or its potential underlying mechanisms of action. In the present study, the effect of juglone on the EMT of prostate cancer cells was investigated. Transwell assays were used to demonstrate that juglone inhibits the migration and invasion of the prostate cancer (PC) LNCaP and LNCaPAI cell lines. Results from western blot analysis demonstrated that juglone increases the expression of the epithelial marker Ecadherin while decreasing the expression of mesenchymal markers (Ncadherin and Vimentin) in a dosedependent manner. The data from the present study also revealed that juglone downregulates the expression of Snail, a repressor of Ecadherin and an inducer of EMT. Furthermore, juglone prevented inactivation of glycogen synthase kinase3β (GSK3β), an endogenous inhibitor of Snail in a dosedependent manner. Lithium chloride (LiCl), a GSK3β inhibitor, prevented juglonemediated downregulation of Snail expression and upregulation of Ecadherin. In addition, phosphorylation and subsequent activation of protein kinase B (Akt), which is known to phosphorylate GSK3β at serine 9 (Ser9), leading to its inhibition, were significantly decreased by juglone in LNCaP and LNCaPAI cells. Inhibition of the phosphatidylinositol4,5bisphosphate 3kinase (PI3K)/Akt pathway by LY294002 augmented juglonemediated GSK3β activity by inhibiting Ser9 phosphorylation. These findings indicated that juglone suppresses EMT via the Akt/GSK3β/Snail pathway, consequently decreasing the invasiveness of PC cells.
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Document Type: Research Article

Affiliations: 1: Department of Immunology, Jilin Medical University, Jilin City, Jilin 132013, P.R. China 2: Department of Urology Surgery, Affiliated Hospital of Jilin Medical University, Jilin City, Jilin 132013, P.R. China

Publication date: January 1, 2018

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  • Oncology Letters is a monthly, peer-reviewed journal, available in print and online, that focuses on all aspects of clinical oncology, as well as in vitro and in vivo experimental model systems relevant to the mechanisms of disease.

    The principal aim of Oncology Letters is to provide the prompt publication of original studies of high quality that pertain to clinical oncology, chemotherapy, oncogenes, carcinogenesis, metastasis, epidemiology and viral oncology in the form of original research, reviews and case reports.
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