ArticleMolecular cancer2014
Inhibition of the checkpoint kinase Chk1 induces DNA damage and cell death in human Leukemia and Lymphoma cells.
Article in Molecular cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- Synthetic Lethal Combinations of DNA Repair Inhibitors and Genotoxic Agents to Target High-Risk Diffuse Large B Cell Lymphoma.Hematological oncology · 2025Article
- Targeting the DNA damage response in hematological malignancies.Frontiers in oncology · 2024Review
- Genotoxicity of Novel Pyrazolo[4,3-International journal of molecular sciences · 2023Article
- Proteomic profiling based classification of CLL provides prognostication for modern therapy and identifies novel therapeutic targets.Blood cancer journal · 2022Article
- Chk1 inhibitor-induced DNA damage increases BFL1 and decreases BIM but does not protect human cancer cell lines from Chk1 inhibitor-induced apoptosis.American journal of cancer research · 2022Article
- Checkpoint Kinase 1 (Chk1) inhibition fails to activate the Stimulator of Interferon Genes (STING) innate immune signalling in a human coculture cancer system.Molecular biomedicine · 2021Article
- Gut Microbiome Critically Impacts PCB-induced Changes in Metabolic Fingerprints and the Hepatic Transcriptome in Mice.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Novel CHK1 inhibitor MU380 exhibits significant single-agent activity in TP53-mutated chronic lymphocytic leukemia cells.Haematologica · 2019Article
- Inhibition of CHK 1 (Checkpoint Kinase 1) Elicits Therapeutic Effects in Pulmonary Arterial Hypertension.Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- lncRNA CASC9 positively regulates CHK1 to promote breast cancer cell proliferation and survival through sponging the miR‑195/497 cluster.International journal of oncology · 2019Article
- Article
- Article
- Alternative Chk1-independent S/M checkpoint in somatic cells that prevents premature mitotic entry.Medical oncology (Northwood, London, England) · 2017Article
- Review
- Modification of tumour cell metabolism modulates sensitivity to Chk1 inhibitor-induced DNA damage.Scientific reports · 2017Article
- Inhibition of Chk1 with the small molecule inhibitor V158411 induces DNA damage and cell death in an unperturbed S-phase.Oncotarget · 2016Article
- Deregulation of vital mitotic kinase-phosphatase signaling in hematopoietic stem/progenitor compartment leads to cellular catastrophe in experimental aplastic anemia.Molecular and cellular biochemistry · 2016Article
- Tumour growth environment modulates Chk1 signalling pathways and Chk1 inhibitor sensitivity.Scientific reports · 2016Article
- Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53-mutated B-lymphoid cells.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChk1 forms a core component of the DNA damage response and small molecule inhibitors are currently being investigated in the clinic as cytotoxic chemotherapy potentiators. Recent evidence suggests that Chk1 inhibitors may demonstrate significant single agent activity in tumors with specific DNA repair defects, a constitutively activated DNA damage response or oncogene induced replicative stress.
methodsGrowth inhibition induced by the small molecule Chk1 inhibitor V158411 was assessed in a panel of human leukemia and lymphoma cell lines and compared to cancer cell lines derived from solid tumors. The effects on cell cycle and DNA damage response markers were further evaluated.
resultsLeukemia and lymphoma cell lines were identified as particularly sensitive to the Chk1 inhibitor V158411 (mean GI50 0.17 μM) compared to colon (2.8 μM) or lung (6.9 μM) cancer cell lines. Chk1 inhibition by V158411 in the leukemia and lymphoma cell lines induced DNA fragmentation and cell death that was both caspase dependent and independent, and prevented cells undergoing mitosis. An analysis of in vitro pharmacodynamic markers identified a dose dependent decrease in Chk1 and cyclin B1 protein levels and Cdc2 Thr15 phosphorylation along with a concomitant increase in H2AX phosphorylation at Ser139 following V158411 treatment.
conclusionsThese data support the further evaluation of Chk1 inhibitors in hematopoietic cancers as single agents as well as in combination with standard of care cytotoxic drugs.
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