Article ; Online: Identification of a novel form of caspase-independent cell death triggered by BH3-mimetics in diffuse large B-cell lymphoma cell lines.
2024 Volume 15, Issue 4, Page(s) 266
Abstract: BH3-mimetics represent promising anti-cancer agents in tumors that rely on the anti-apoptotic function of B-Cell Lymphoma 2 (BCL2) proteins, particularly in leukemia and lymphoma cells primed for apoptosis. Mechanistically, BH3-mimetics may displace pro- ... ...
| Abstract | BH3-mimetics represent promising anti-cancer agents in tumors that rely on the anti-apoptotic function of B-Cell Lymphoma 2 (BCL2) proteins, particularly in leukemia and lymphoma cells primed for apoptosis. Mechanistically, BH3-mimetics may displace pro-apoptotic binding partners thus inducing BAX/BAK-mediated mitochondrial permeabilization followed by cytochrome c release, activation of the caspase cascade and apoptosis. Here, we describe a novel mode of caspase-independent cell death (CICD) induced by BH3-mimetics in a subset of diffuse large B-cell lymphoma (DLBCL) cells. Of note, rather than occurring via necroptosis, CICD induced immediately after mitochondrial permeabilization was associated with transcriptional reprogramming mediated by activation of c-Jun N-terminal Kinase (JNK) signaling and Activator Protein 1 (AP1). Thereby, CICD resulted in the JNK/AP1-mediated upregulation of inflammatory chemokines and increased migration of cytotoxic Natural Killer (NK) cells. Taken together, our study describes a novel mode of CICD triggered by BH3-mimetics that may alter the immune response towards dying cells. |
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| MeSH term(s) | Humans ; bcl-2-Associated X Protein/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; Apoptosis ; Antineoplastic Agents/pharmacology ; Caspases ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Cell Line ; Proto-Oncogene Proteins c-bcl-2/metabolism |
| Chemical Substances | bcl-2-Associated X Protein ; bcl-2 Homologous Antagonist-Killer Protein ; Antineoplastic Agents ; Caspases (EC 3.4.22.-) ; Proto-Oncogene Proteins c-bcl-2 |
| Language | English |
| Publishing date | 2024-04-15 |
| Publishing country | England |
| Document type | Journal Article |
| ZDB-ID | 2541626-1 |
| ISSN | 2041-4889 ; 2041-4889 |
| ISSN (online) | 2041-4889 |
| ISSN | 2041-4889 |
| DOI | 10.1038/s41419-024-06652-3 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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