Proteomic analysis reveals trilaciclib-induced senescence Journal Article
| Authors: | Hermosilla-Trespaderne, M.; Hu-Yang, M. X.; Dannoura, A.; Frey, A. M.; George, A. L.; Trost, M.; Marín-Rubio, J. L. |
| Article Title: | Proteomic analysis reveals trilaciclib-induced senescence |
| Abstract: | 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. © 2024 THE AUTHORS. Published by Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology. |
| Keywords: | protein expression; human cell; flow cytometry; cell proliferation; mass spectrometry; metabolism; cell death; cell viability; cell cycle; cell cycle progression; imatinib; protein kinase inhibitor; drug effect; cell line, tumor; chronic myeloid leukemia; pyrimidines; proteomics; cancer therapy; acute lymphoblastic leukemia; protein kinase inhibitors; tumor cell line; western blotting; beta galactosidase; imaging; bone marrow cell; hematopoietic stem cell; senescence; autophagy; pyrroles; pyrimidine derivative; cell cycle phase; fused heterocyclic rings; drug sensitivity; cell aging; myeloproliferative neoplasm; myeloma; cyclin dependent kinase 4; pyrrole derivative; non-hodgkin lymphoma; cyclin-dependent kinase 4; cyclin dependent kinase 6; non small cell lung cancer; cyclin-dependent kinase 6; short tandem repeat; k562 cells; electrospray; myeloma cell; acute myeloid leukemia; liquid chromatography-mass spectrometry; procedures; cellular senescence; autophagic cell death; cdk4 protein, human; humans; human; article; palbociclib; cancer cell line; cell viability assay; ic50; clustered regularly interspaced short palindromic repeat; gene set enrichment analysis; crispr-cas9 system; oxygen consumption rate; a-549 cell line; jurkat cell line; bridged bicyclo compounds, heterocyclic; asciminib; mrna expression level; kegg; lung non-small cell carcinoma cell line; k-562 cell line; autophagy (cellular); u-937 cell line; apoptosis assay; pyridinium compounds; trilaciclib; pyridinium derivative; blood cancer cell line; collisionally activated dissociation; nci-h929 cell line |
| Journal Title: | Molecular & Cellular Proteomics |
| Volume: | 23 |
| Issue: | 6 |
| ISSN: | 1535-9476 |
| Publisher: | Amer Soc Biochemistry Molecular Biology Inc |
| Date Published: | 2024-06-01 |
| Start Page: | 100778 |
| Language: | English |
| DOI: | 10.1016/j.mcpro.2024.100778 |
| PUBMED: | 38679389 |
| PROVIDER: | scopus |
| PMCID: | PMC11141265 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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