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- W4307777222 abstract "<h3>Abstract</h3> Background/Aim: Evidence for the relevance of Epstein–Barr virus (EBV) in various types of cancer has expanded; however, the definitive mechanism of EBV-induced oncogenesis remains ambiguous. The purpose of this study was to identify the relevance of aurora kinases in EBV-induced carcinogenesis, and the cellular responses to danusertib, a pan-aurora kinase inhibitor. The underlying signaling mechanism in EBV-transformed B-cells was also investigated. Materials and Methods: Western blotting was performed on EBV-transformed B-cells and EBV-positive lymphoma cells to identify aurora kinase expression. Cellular responses of EBV-transformed B-cells to danusertib were investigated using AlamaBlue assay and apoptosis analysis. To evaluate the underlying signaling mechanisms of danusertib-induced apoptosis, cleavage of caspase cascade molecules, endoplasmic reticulum (ER) stress-associated molecule activation, and intracellular Ca<sup>2+</sup> levels were evaluated using western blotting, flow cytometry, and inhibition assays. Results: Expression of both aurora kinase A and B was gradually increased in EBV-infected B-cells and two EBV-positive B lymphoma cell lines. Danusertib significantly suppressed EBV-transformed B-cell proliferation in a dose-dependent manner. Danusertib induced apoptosis and cell cycle arrest through disruption of mitochondrial membrane potential in EBV-transformed B-cells in a dose-dependent and time-dependent manner. Moreover, danusertib induced cleavage of caspases, ER stress-associated molecule activation, and intracellular Ca<sup>2+</sup> release from ER to cytoplasm in EBV-transformed B-cells, while BAPTA-AM, a calcium chelator, inhibited danusertib-induced apoptosis. Conclusion: Danusertib treatment led to apoptosis of EBV-transformed B-cells through ER stress-associated proteins and mitochondrial caspase activation. These results suggest that aurora kinases may be valuable targets for potential therapeutic agents against EBV-associated carcinoma." @default.
- W4307777222 created "2022-11-05" @default.
- W4307777222 creator A5030707488 @default.
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- W4307777222 date "2022-10-26" @default.
- W4307777222 modified "2023-09-24" @default.
- W4307777222 title "Pan-Aurora Kinase Inhibitor Danusertib Induces Apoptosis of Epstein–Barr Virus-transformed B-Cells Through Caspase and Endoplasmic Reticulum Stress Signaling" @default.
- W4307777222 doi "https://doi.org/10.21873/anticanres.16033" @default.
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