Proteomic Analysis Reveals Trilaciclib-Induced Senescence
Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. Whil...
| Authors: | , , , , , , |
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| Format: | article |
| Publication Date: | 2024 |
| Country: | España |
| Institution: | Universidad Francisco de Vitoria |
| Repository: | DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria |
| Language: | English |
| OAI Identifier: | oai:ddfv.ufv.es:10641/7225 |
| Online Access: | https://hdl.handle.net/10641/7225 |
| Access Level: | Open access |
| Keyword: | Analytical Chemistry Biochemistry Molecular Biology SDG 3 - Good Health and Well-being Yes yes |
| Summary: | Trilaciclib, a cyclin-dependent kinase 4/6 inhibitor, was approved as a myeloprotective agent for protecting bone marrow from chemotherapy-induced damage in extensive-stage small cell lung cancer. This is achieved through the induction of a temporary halt in the cell cycle of bone marrow cells. While it has been studied in various cancer types, its potential in hematological cancers remains unexplored. This research aimed to investigate the efficacy of trilaciclib in hematological cancers. Utilizing mass spectrometry-based proteomics, we examined the alterations induced by trilaciclib in the chronic myeloid leukemia cell line, K562. Interestingly, trilaciclib promoted senescence in these cells rather than cell death, as observed in acute myeloid leukemia, acute lymphoblastic leukemia, and myeloma cells. In K562 cells, trilaciclib hindered cell cycle progression and proliferation by stabilizing cyclin-dependent kinase 4/6 and downregulating cell cycle–related proteins, along with the concomitant activation of autophagy pathways. Additionally, trilaciclib-induced senescence was also observed in the nonsmall cell lung carcinoma cell line, A549. These findings highlight trilaciclib's potential as a therapeutic option for hematological cancers and underscore the need to carefully balance senescence induction and autophagy modulation in chronic myeloid leukemia treatment, as well as in nonsmall cell lung carcinoma cell line. |
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