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Lookup NU author(s): Marina Hermosilla, Dr Abeer Dannoura, Dr Andrew FreyORCiD, Amy George, Professor Matthias TrostORCiD, Dr Jose Luis Marin-RubioORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology.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.
Author(s): Hermosilla-Trespaderne M, Hu-Yang MX, Dannoura A, Frey AM, George AL, Trost M, Marin-Rubio JL
Publication type: Article
Publication status: Published
Journal: Molecular and Cellular Proteomics
Year: 2024
Volume: 23
Issue: 6
Print publication date: 01/06/2024
Online publication date: 26/04/2024
Acceptance date: 13/03/2024
Date deposited: 15/07/2024
ISSN (print): 1535-9476
ISSN (electronic): 1535-9484
Publisher: American Society for Biochemistry and Molecular Biology Inc.
URL: https://doi.org/10.1016/j.mcpro.2024.100778
DOI: 10.1016/j.mcpro.2024.100778
Data Access Statement: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (50) via the PRIDE partner repository (51) with the dataset identifier: PXD045276.
PubMed id: 38679389
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