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Regulation of valproic acid induced EMT by AKT/GSK3β/β-catenin signaling pathway in triple negative breast cancer

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Abstract

Valproic acid (VPA) is a selective histone deacetylation (HDAC) inhibitor and exerts anti-cancer properties in different types of cancer. The epithelial-to-mesenchymal transition (EMT) mediating by different signaling cascade can be a potential target in aggressive human cancers. Therefore, we aimed to clarified the unravel relationship between AKT/GSK3β/β-catenin signalling pathway and VPA-induced EMT in triple negative breast cancer (TNBC). The cytotoxicity of VPA in MDA-MB-231 TNBC and MCF-10A control cells was evaluated. Alterations in the expression levels of Snail, E-cadherin, AKT, GSK3β, β-catenin were analyzed by RT-PCR. Additionally, Annexin V, cell cycle and wound healing assays were performed. Our results showed that VPA remarkably inhibited the growth of TNBC cell and triggered apoptotic cell death through G0/G1 arrest. Furthermore, VPA increased cell migration and activated the EMT process through significantly increasing Snail expression and in turn downregulation of E-cadherin and GKS3β levels. However, the level of AKT and β-catenin was reduced after treatment of VPA. Our data showed that VPA induced EMT process and cell migration in TNBC cells. However, AKT/GSK3β/β-catenin signaling pathway did not mediate EMT activation.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey

    Zeynep Ozman

  2. Medical Biochemistry Laboratory, Kızılcahamam State Hospital, Ankara, Turkey

    Betul Ozbek Iptec

  3. Department of Histology and Embryology, Faculty of Medicine, Sakarya University, Sakarya, Turkey

    Elvan Sahin

  4. Department of Medical Biology, Faculty of Medicine, Sakarya University, Sakarya, Turkey

    Gamze Guney Eskiler, Asuman Deveci Ozkan & Suleyman Kaleli

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  1. Zeynep Ozman
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  2. Betul Ozbek Iptec
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  5. Asuman Deveci Ozkan
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Contributions

ZO, BOI, ES,GGE, ADO and SK conceptualized, design and coordinated the investigation. ZO, BOI, GGE and ADO conducted the analyses and coordinated the investigation. ES an SK analyzed the data and carried out the statistical analysis. All authors participated in writing, reading and approval of the final manuscript.

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Correspondence to Asuman Deveci Ozkan.

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Ozman, Z., Ozbek Iptec, B., Sahin, E. et al. Regulation of valproic acid induced EMT by AKT/GSK3β/β-catenin signaling pathway in triple negative breast cancer. Mol Biol Rep 48, 1335–1343 (2021). https://doi.org/10.1007/s11033-021-06173-8

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  • DOI: https://doi.org/10.1007/s11033-021-06173-8

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