{"doi":"10.1038/cddis.2016.254","title":"Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme","abstract":"<jats:title>Abstract</jats:title><jats:p>The nitric oxide (NO) donor JS-K is specifically activated by glutathione S-transferases (GSTs) in GST-overexpressing cells. We have shown the induction of cell death in glioblastoma multiforme (GBM) cells at high JS-K doses but the mechanism remains unclear. The aim of this study was to determine whether NO-induced cell death is triggered by induction of apoptotic or necrotic pathways. For the first time, we demonstrate that NO induces cell death via mitotic catastrophe (MC) with non-apoptotic mechanisms in GBM cells. Moreover, the level of morphological changes indicating MC correlates with increased necrosis. Therefore, we conclude that MC is the main mechanism by which GBM cells undergo cell death after treatment with JS-K associated with necrosis rather than apoptosis. In addition, we show that PARP1 is not an exclusive marker for late apoptosis but is also involved in MC. Activating an alternative way of cell death can be useful for the multimodal cancer therapy of GBM known for its strong anti-apoptotic mechanisms and drug resistance.</jats:p>","journal":"Cell Death &amp; Disease","year":2016,"id":605327,"datarank":0.47032413238937254,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.0,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1553471,"name":"Nadja Osterberg","orcid":null,"position":1,"is_corresponding":false},{"id":1553472,"name":"Joseph E Saavedra","orcid":null,"position":2,"is_corresponding":false},{"id":1553473,"name":"Astrid Weyerbrock","orcid":"0000-0001-9060-4462","position":3,"is_corresponding":false},{"id":1553470,"name":"Jessica Günzle","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme","abstract":"<jats:title>Abstract</jats:title><jats:p>The nitric oxide (NO) donor JS-K is specifically activated by glutathione S-transferases (GSTs) in GST-overexpressing cells. We have shown the induction of cell death in glioblastoma multiforme (GBM) cells at high JS-K doses but the mechanism remains unclear. The aim of this study was to determine whether NO-induced cell death is triggered by induction of apoptotic or necrotic pathways. For the first time, we demonstrate that NO induces cell death via mitotic catastrophe (MC) with non-apoptotic mechanisms in GBM cells. Moreover, the level of morphological changes indicating MC correlates with increased necrosis. Therefore, we conclude that MC is the main mechanism by which GBM cells undergo cell death after treatment with JS-K associated with necrosis rather than apoptosis. In addition, we show that PARP1 is not an exclusive marker for late apoptosis but is also involved in MC. Activating an alternative way of cell death can be useful for the multimodal cancer therapy of GBM known for its strong anti-apoptotic mechanisms and drug resistance.</jats:p>","is_dataset_classified":null,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"27584787","pmcid":"PMC5059858","openalex_id":"https://openalex.org/W2515363884","authors":[],"funders":[],"total_grants":0,"fwci":1.7637,"citation_percentile":0.8499835,"influential_citations":0,"citation_trend":[{"year":2017,"count":4},{"year":2019,"count":7},{"year":2020,"count":1},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2024,"count":1},{"year":2025,"count":3},{"year":2026,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/cddis2016254.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/cddis2016254.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/cddis2016254","host_type":"publisher"},{"url":"https://doi.org/10.1038/cddis.2016.254","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/27584787","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5059858","host_type":"repository"},{"url":"https://freidok.uni-freiburg.de/data/12331","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5059858","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5059858?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Glutathione Transferases and Polymorphisms","Redox biology and oxidative stress","Genomics, phytochemicals, and oxidative stress","Adenosine Triphosphate","Apoptosis","Azo Compounds","Blotting, Western","Caspases","Cell Line, Tumor","Cyclic GMP","Enzyme Activation","Flow Cytometry","Glioblastoma","Humans","In Situ Nick-End Labeling","Mitosis","Necrosis","Nitric Oxide","Piperazines","Poly(ADP-ribose) Polymerases","Proto-Oncogene Proteins c-akt","Time Factors"],"mesh_terms":["Adenosine Triphosphate","Azo Compounds","Enzyme Activation","Flow Cytometry","Glioblastoma","Cyclic GMP","Humans","Mitosis","Necrosis","Nitric Oxide","Piperazines","Poly(ADP-ribose) Polymerases","Time Factors","Blotting, Western","Apoptosis","Caspases","In Situ Nick-End Labeling","Cell Line, Tumor","Proto-Oncogene Proteins c-akt"],"keywords":["Programmed cell death","Mitotic catastrophe","Apoptosis","Necrosis","PARP1","Mitosis","Nitric oxide","Cancer research","Tumor necrosis factor alpha","Biology","Cell biology","Cell","Glutathione","Poly ADP ribose polymerase","Immunology","Biochemistry","Genetics","Polymerase","Enzyme"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T02:11:53.151159Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}