The Role of Bcl-2 and Beclin-1 Complex in "Switching" between Apoptosis and Autophagy in Human Glioma Cells upon LY294002 and Sorafenib Treatment
BACKGROUND: Gliomas are the most malignant tumors of the central nervous system. One of the factors in their high drug resistance is avoiding programmed death (PCD) induction. This is related to the overexpression of intracellular survival pathways: PI3K-Akt/PKB-mTOR and Ras-Raf-MEK-ERK. Apoptosis and autophagy are co-existing processes due to the interactions between Bcl-2 and beclin-1 proteins. Their complex may be a molecular "toggle-switch" between PCD types. The aim of this research was to investigate the role of Bcl-2:beclin-1 complex in glioma cell elimination through the combined action of LY294002 and sorafenib.
METHODS: Drug cytotoxicity was estimated with an MTT test. The type of cell death was evaluated using variant microscopy techniques (fluorochrome staining, immunocytochemistry, and transmission electron microscopy), as well as the Bcl-2:beclin-1 complex formation and protein localization. Molecular analysis of PCD indicators was conducted through immunoblotting, immunoprecipitation, and ELISA testing. SiRNA was used to block Bcl-2 and beclin-1 expression.
RESULTS: The results showed the inhibitors used in simultaneous application resulted in Bcl-2:beclin-1 complex formation and apoptosis becoming dominant. This was accompanied by changes in the location of the tested proteins.
CONCLUSIONS: "Switching" between apoptosis and autophagy using PI3K and Raf inhibitors with Bcl-2:beclin-1 complex formation opens new therapeutic perspectives against gliomas.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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Enthalten in: |
Cells - 12(2023), 23 vom: 21. Nov. |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zając, Adrian [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 12.01.2024 Date Revised 10.02.2024 published: Electronic Citation Status MEDLINE |
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doi: |
10.3390/cells12232670 |
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funding: |
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PPN (Katalog-ID): |
NLM365579157 |
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520 | |a BACKGROUND: Gliomas are the most malignant tumors of the central nervous system. One of the factors in their high drug resistance is avoiding programmed death (PCD) induction. This is related to the overexpression of intracellular survival pathways: PI3K-Akt/PKB-mTOR and Ras-Raf-MEK-ERK. Apoptosis and autophagy are co-existing processes due to the interactions between Bcl-2 and beclin-1 proteins. Their complex may be a molecular "toggle-switch" between PCD types. The aim of this research was to investigate the role of Bcl-2:beclin-1 complex in glioma cell elimination through the combined action of LY294002 and sorafenib | ||
520 | |a METHODS: Drug cytotoxicity was estimated with an MTT test. The type of cell death was evaluated using variant microscopy techniques (fluorochrome staining, immunocytochemistry, and transmission electron microscopy), as well as the Bcl-2:beclin-1 complex formation and protein localization. Molecular analysis of PCD indicators was conducted through immunoblotting, immunoprecipitation, and ELISA testing. SiRNA was used to block Bcl-2 and beclin-1 expression | ||
520 | |a RESULTS: The results showed the inhibitors used in simultaneous application resulted in Bcl-2:beclin-1 complex formation and apoptosis becoming dominant. This was accompanied by changes in the location of the tested proteins | ||
520 | |a CONCLUSIONS: "Switching" between apoptosis and autophagy using PI3K and Raf inhibitors with Bcl-2:beclin-1 complex formation opens new therapeutic perspectives against gliomas | ||
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700 | 1 | |a Filipek, Kamil |e verfasserin |4 aut | |
700 | 1 | |a Deryło, Kamil |e verfasserin |4 aut | |
700 | 1 | |a Langner, Ewa |e verfasserin |4 aut | |
700 | 1 | |a Pawelec, Jarosław |e verfasserin |4 aut | |
700 | 1 | |a Wasiak, Magdalena |e verfasserin |4 aut | |
700 | 1 | |a Ścibiorski, Mateusz |e verfasserin |4 aut | |
700 | 1 | |a Rzeski, Wojciech |e verfasserin |4 aut | |
700 | 1 | |a Tchórzewski, Marek |e verfasserin |4 aut | |
700 | 1 | |a Reichert, Michał |e verfasserin |4 aut | |
700 | 1 | |a Jakubowicz-Gil, Joanna |e verfasserin |4 aut | |
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