ArticleActa pharmacologica Sinica2012
Imatinib induces H2AX phosphorylation and apoptosis in chronic myelogenous leukemia cells in vitro via caspase-3/Mst1 pathway.
Article in Acta pharmacologica Sinica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 45 citations in OpenAlex.
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- Porcine Enteric Coronavirus PEDV Induces the ROS-ATM and Caspase7-CAD-γH2AX Signaling Pathways to Foster Its Replication.Viruses · 2022Article
- 1,4-Naphthoquinone (CNN1) Induces Apoptosis through DNA Damage and Promotes Upregulation ofInternational journal of molecular sciences · 2022Article
- Blocking PARP activity with the inhibitor veliparib enhances radiotherapy sensitivity in endometrial carcinoma.Journal of clinical laboratory analysis · 2022Article
- The emerging role of ISWI chromatin remodeling complexes in cancer.Journal of experimental & clinical cancer research : CR · 2021Review
- BAZ1B the Protean Protein.Genes · 2021Review
- C-Abl is not actıvated in DNA damage-induced and Tap63-mediated oocyte apoptosıs in human ovary.Cell death & disease · 2018Article
- Melatonin Regulates Apoptosis and Autophagy Via ROS-MST1 Pathway in Subarachnoid Hemorrhage.Frontiers in molecular neuroscience · 2018Article
- Adhesion to stromal cells mediates imatinib resistance in chronic myeloid leukemia through ERK and BMP signaling pathways.Scientific reports · 2017Article
- Influence of selected anti-cancer drugs on the induction of DNA double-strand breaks and changes in gene expression in human hepatoma HepG2 cells.Environmental science and pollution research international · 2016Article
- Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses.Molecular biology of the cell · 2016Article
- Early protective role of MST1 knockdown in response to experimental diabetic nephropathy.American journal of translational research · 2016Article
- Regulation of Bim in Health and Disease.Oncotarget · 2015Review
- Resveratrol induces apoptosis of human chronic myelogenous leukemia cells in vitro through p38 and JNK-regulated H2AX phosphorylation.Acta pharmacologica Sinica · 2015Article
- Prediction of functional phosphorylation sites by incorporating evolutionary information.Protein & cell · 2012Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimHistone H2AX is a novel tumor suppressor and its phosphorylation at the C terminus (Ser139 and Tyr142) is required for tumor cell apoptosis. The aim of the present study was to elucidate the mechanisms underlying imatinib-induced C-terminal phosphorylation of H2AX in chronic myelogenous leukemia cells in vitro.
methodsBCR-ABL-positive K562 cells were used. Microscopy, Western blotting and flow cytometry were used to study the signaling pathways that regulate imatinib-induced H2AX phosphorylation and the apoptotic mechanisms.
resultsTreatment of K562 cells with imatinib (1-8 μmol/L) induced phosphorylation of H2AX at Ser139 and Tyr142 in time- and dose-dependent manners. In contrast, imatinib at the same concentrations did not affect H2AX acetylation at Lys 5, and the acetylated H2AX maintained a higher level in the cells. Meanwhile, imatinib (1-8 μmol/L) activated caspase-3 and its downstream mammalian STE20-like kinase 1 (Mst1), and induced apoptosis of K562 cells. The caspase-3 inhibitor Z-VAD (40 μmol/L) reduced imatinib-induced H2AX phosphorylation at Ser139 and Tyr142 and blocked imatinib-induced apoptosis of K562 cells. Imatinib (4 μmol/L) induced expression of Williams-Beuren syndrome transcription factor (WSTF), but not wild-type p53-induced phosphatase 1 (Wip1) in K562 cells.
conclusionThe caspase-3/Mst1 pathway is required for H2AX C-terminal phosphorylation at Ser139 and Tyr142 and subsequent apoptosis in Bcr-Abl-positive K562 cells induced by imatinib.
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