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• W4380740841 abstract "Abstract Introduction: Toona sinensis is a traditional Chinese medicine commonly used in South-East Asia. The aqueous extracts of T. sinensis leaves (TSL) exhibit anticancer effects in various types of cancer. In this study, we assessed the effectiveness of TSL treatment for glioblastoma multiforme (GBM). Methods After treating A172 and U251 GBM with TSL, cell cycle and apoptotic cells were evaluated by flow cytometry, as well as anti-proliferative efficacy by MTT assay. Reactive oxygen species (ROS) and ATP production were quantified by CellROX, Dihydroethidium (DHE) and Tetramethylrhodamine methyl ester (TMRM). Apoptosis and MEK/ERK pathway related protein levels were detected by western blot. Results Gallic acid was demonstrated the major effective component in aqueous extracts in TSL under HPLC system and it could penetrate across blood-brain barrier. TSL treatment inhibited cell growth and proliferation and exerted cytotoxic effect in A172 and U251 GBM cells. Flow cytometry analysis revealed cell cycle arrest at G2/M and apoptotic cells. Mitochondrial dysfunction presented with excessive reactive oxygen species (ROS) and decreased ATP production via blockage of electron transport chain (ETC) complexes, leading to ROS-regulated mitochondrial dysfunction. Furthermore, Western blotting data indicated that TSL treatment upregulated the levels of Bax and Puma and downregulated the level of Bcl-2. Moreover, cleaved caspase-3, cleaved caspase-9, and cleaved PARP were induced to illustrate mitochondria-mediated apoptosis and caspase-dependent pathway under TSL treatment in two GBM cells. Finally, U0126 as an inhibitor of MEK/ERK kinase was applied to demonstrate that the MEK/ERK pathway was responsible for the inhibition of ROS-regulated mitochondrial dysfunction and promoted apoptosis. Conclusion TSL treatment suppressed MEK/ERK activation to induce apoptosis through antioxidant effect in GBM cells. This mechanism may provide a therapeutic potential in GBM therapy." @default.
• W4380740841 created "2023-06-16" @default.
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• W4380740841 date "2023-06-15" @default.
• W4380740841 modified "2023-09-30" @default.
• W4380740841 title "Identify Cytotoxic Activity in Phenolic Aqueous Extracts of Toona Sinensis Leaves via Mitochondrial Dysfunction Through the MEK/ERK Signaling Pathway in Human Glioblastoma Cells" @default.
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• W4380740841 doi "https://doi.org/10.21203/rs.3.rs-2649668/v1" @default.
• W4380740841 hasPublicationYear "2023" @default.
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