title: Inhibition of drug-induced DNA fragmentation, but not cell death, of glioma cells by non-caspase protease inhibitors.
abstract: The role of non-caspase protease activation in drug-induced cell death of glioma cells was examined. Neither calpain inhibitors I or II, phenylmethylsulfonyl fluoride (PMSF), Nalpha -p-tosyl-L-lysine chloromethyl ketone (TLCK), N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), E64, leupeptin nor pepstatin inhibit the cytotoxicity of vincristine, cisplatin, doxorubicin, cytarabine, camptothecin, BCNU or VM26 in two malignant glioma cell lines, T98G and LN-229. However, DNA fragmentation induced by VM26 is inhibited by calpain inhibitor I, PMSF, TLCK and TPCK, and that induced by camptothecin by calpain inhibitors I and II and TPCK. Moreover, protease inhibitors fail to abrogate CD95 ligand-induced apoptosis even though DNA fragmentation is attenuated by calpain inhibitor II and TPCK. Thus, non-caspase protease activation is not required for drug-induced apoptosis of glioma cells. Protease inhibitor-mediated inhibition of DNA fragmentation operates downstream of the commitment point for cell death.
authors.affiliation: Department of Neurology, University of Tübingen, School of Medicine, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Eitel
authors.forename: B
authors.initials: B
authors.lastname: Wagenknecht
authors.forename: M
authors.initials: M
authors.lastname: Weller
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016923:Cell Death / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004336:Drug Antagonism; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011480:Protease Inhibitors