title: Cell death induced in a human glioblastoma cell line by p(65)+Be neutrons combined with cisplatin.
abstract: High linear energy transfer (LET) radiation have the ability to kill cancer cells resistant to conventional radiotherapy. On the other hand, protocols combining radiotherapy and chemotherapy are effective in eradicating certain inoperable cancers. In this study, we investigated the cytotoxicity of a co-treatment with fast neutrons and cisplatin in a human glioblastoma cell line, U-87. Cells cultured in vitro were irradiated with p(65)+Be neutrons in the presence of cisplatin. Cell survival and the induction of apoptosis and premature senescence were assessed at different time intervals thereafter, using a variety of methods. A marked reinforcement of the cytotoxicity was obtained when irradiation and cisplatin were associated. This reflected both an amplification of the apoptotic process and the induction of premature cell senescence. The efficiency of a combination between fast neutrons and cisplatin in inducing cell death in U-87 is more than additive. The present data concur with those we previously reported in a mouse lymphoma and suggest the potential utility of platinum compounds as adjuncts to future cancer therapy protocols using high-LET radiation.
authors.affiliation: Laboratoire de Cancérologie Expérimentale et de Radiobiologie, EA-3430, IRCAD, Hôpitaux Universitaires, 1 place de l'Hôpital, F-67091 Strasbourg, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Benzina
authors.forename: Barbara
authors.initials: B
authors.lastname: Fischer
authors.forename: Anne
authors.initials: A
authors.lastname: Miternique-Grosse
authors.forename: Patrick
authors.initials: P
authors.lastname: Dufour
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Denis
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bergerat
authors.forename: John
authors.initials: J
authors.lastname: Gueulette
authors.forename: Pierre
authors.initials: P
authors.lastname: Bischoff
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology*; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005214:Fast Neutrons; D005909:Glioblastoma / Q000201:enzymology / Q000473:pathology; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D003470:Culture Media; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002945:Cisplatin