title: Artesunate enhances the antiproliferative effect of temozolomide on U87MG and A172 glioblastoma cell lines.
abstract: As chemotherapy with temozolomide is far from providing satisfactory clinical outcomes for patients with glioblastoma, more efficient drugs and drug combinations are urgently needed. The anti-malarial artesunate was previously shown to exert a profound cytotoxic effect on various tumor cell lines including those derived from glioblastoma. In the current study, we sought to examine the antiproliferative effect of a combination of temozolomide and artesunate on two different established human glioblastoma cell lines. The IC50 and IC25 were determined for temozolomide and artesunate in U87MG and A172 glioblastoma cell lines after 144 h of continuous drug exposure. The antiproliferative effect of combining both agents at IC50/IC50 and IC25/IC25 was determined by a cell viability assay. Moreover, necrosis and apoptosis were analyzed by annexin V/PI staining and flow cytometric analysis. In addition, cytostatic effects were examined by carboxyfluorescein diacetate succinimidyl ester staining and subsequent flow cytometry. In both glioblastoma cell lines, artesunate was found to enhance the antiproliferative effect exerted by temozolomide. Moreover, artesunate acted in concert with temozolomide in terms of cytostatic and necrotizing effects. These observations suggest that a combination of artesunate and temozolomide might result in increased cytotoxicity in glioblastoma.
authors: Georg
authors: G
authors: Karpel-Massler
authors: Mike-Andrew
authors: MA
authors: Westhoff
authors: Richard E
authors: RE
authors: Kast
authors: Annika
authors: A
authors: Dwucet
authors: Lisa
authors: L
authors: Nonnenmacher
authors: C Rainer
authors: CR
authors: Wirtz
authors: Klaus-Michael
authors: KM
authors: Debatin
authors: University of Ulm, Department of Neurosurgery, Albert-Einstein-Allee 23, D-89081 Ulm, Germany. georg.karpel@uniklinik-ulm.de.
authors: Marc-Eric
authors: ME
authors: Halatsch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004357:Drug Synergism; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D009336:Necrosis; D000077204:Temozolomide
chemical_list: D000970:Antineoplastic Agents; D037621:Artemisinins; D000077332:Artesunate; D003606:Dacarbazine; D000077204:Temozolomide