title: Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines.
abstract: Artemisinin derivatives are well-tolerated anti-malaria drugs that also exert anti-cancer activity. Here, we investigated artemisinin and its derivatives dihydroartemisinin and artesunate in a panel of chemosensitive and chemoresistant human neuroblastoma cells as well as in primary neuroblastoma cultures. Only dihydroartemisinin and artesunate affected neuroblastoma cell viability with artesunate being more active. Artesunate-induced apoptosis and reactive oxygen species in neuroblastoma cells. Of 16 cell lines and two primary cultures, only UKF-NB-3(r)CDDP(1000) showed low sensitivity to artesunate. Characteristic gene expression signatures based on a previous analysis of artesunate resistance in the NCI60 cell line panel clearly separated UKF-NB-3(r)CDDP(1000) from the other cell lines. l-Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate-cysteine ligase), resensitised in part UKF-NB-3(r)CDDP(1000) cells to artesunate. This finding together with bioinformatic analysis of expression of genes involved in glutathione metabolism showed that this pathway is involved in artesunate resistance. These data indicate that neuroblastoma represents an artesunate-sensitive cancer entity and that artesunate is also effective in chemoresistant neuroblastoma cells.
authors.affiliation: Institut für Medizinische Virologie, Klinikum der J.W. Goethe-Universität, Paul Ehrlich-Strasse 40, 60596 Frankfurt am Main, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.forename: Malte C
authors.initials: MC
authors.lastname: Kleinschmidt
authors.forename: Susanne
authors.initials: S
authors.lastname: Barth
authors.forename: Florian
authors.initials: F
authors.lastname: Rothweiler
authors.forename: Janina
authors.initials: J
authors.lastname: Geiler
authors.forename: Rainer
authors.initials: R
authors.lastname: Breitling
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Hedwig
authors.initials: H
authors.lastname: Deubzer
authors.forename: Olaf
authors.initials: O
authors.lastname: Witt
authors.forename: Jörg
authors.initials: J
authors.lastname: Kreuter
authors.forename: Hans Wilhelm
authors.initials: HW
authors.lastname: Doerr
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Cinatl
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics / Q000473:pathology*; D018384:Oxidative Stress
chemical_list: D037621:Artemisinins; D000077332:Artesunate