title: Artesunate induces necrotic cell death in schwannoma cells.
abstract: Established as a potent anti-malaria medicine, artemisinin-based drugs have been suggested to have anti-tumour activity in some cancers. Although the mechanism is poorly understood, it has been suggested that artemisinin induces apoptotic cell death. Here, we show that the artemisinin analogue artesunate (ART) effectively induces cell death in RT4 schwannoma cells and human primary schwannoma cells. Interestingly, our data indicate for first time that the cell death induced by ART is largely dependent on necroptosis. ART appears to inhibit autophagy, which may also contribute to the cell death. Our data in human schwannoma cells show that ART can be combined with the autophagy inhibitor chloroquine (CQ) to potentiate the cell death. Thus, this study suggests that artemisinin-based drugs may be used in certain tumours where cells are necroptosis competent, and the drugs may act in synergy with apoptosis inducers or autophagy inhibitors to enhance their anti-tumour activity.
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth PL6 8BU, UK.
authors.forename: R W
authors.initials: RW
authors.lastname: Button
authors.affiliation: Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: F
authors.initials: F
authors.lastname: Lin
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth PL6 8BU, UK.
authors.forename: E
authors.initials: E
authors.lastname: Ercolano
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth PL6 8BU, UK.
authors.forename: J H
authors.initials: JH
authors.lastname: Vincent
authors.affiliation: Plymouth University Peninsula Dental School, 16 Research Way, Plymouth, Devon PL6 8BU, UK.
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth PL6 8BU, UK.
authors.forename: C O
authors.initials: CO
authors.lastname: Hanemann
authors.affiliation: Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth PL6 8BU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Luo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D001343:Autophagy / Q000187:drug effects; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000494:pharmacology; D004357:Drug Synergism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009336:Necrosis; D009442:Neurilemmoma / Q000473:pathology*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C119724:AGFG1 protein, human; D037621:Artemisinins; D016166:Free Radical Scavengers; D028861:Nuclear Pore Complex Proteins; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D000077332:Artesunate; D002738:Chloroquine