title: Nitric oxide released from JS-K induces cell death by mitotic catastrophe as part of necrosis in glioblastoma multiforme.
abstract: 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.
authors: Department of Neurosurgery, Medical Center-University of Freiburg, Breisacher Str. 64 Freiburg, D-79106, Germany.|University of Freiburg, Faculty of Biology, Schaenzlestr. 1, Freiburg D-79104, Germany.
authors: Jessica
authors: J
authors: Günzle
authors: Department of Neurosurgery, Medical Center-University of Freiburg, Breisacher Str. 64 Freiburg, D-79106, Germany.
authors: Nadja
authors: N
authors: Osterberg
authors: Cancer Inflammation Program, Center for Cancer Research, National Cancer Institute, Building 567, Room 254, Frederick MD 21702, USA.
authors: Joseph E
authors: JE
authors: Saavedra
authors: Department of Neurosurgery, Medical Center-University of Freiburg, Breisacher Str. 64 Freiburg, D-79106, Germany.
authors: Astrid
authors: 0000-0001-9060-4462
authors: A
authors: Weyerbrock
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001391:Azo Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D006152:Cyclic GMP / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005909:Glioblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008938:Mitosis / Q000187:drug effects*; D009336:Necrosis; D009569:Nitric Oxide / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D013997:Time Factors
chemical_list: D001391:Azo Compounds; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D020169:Caspases; D006152:Cyclic GMP