Title:Artesunate Enhances the Antiproliferative Effect of Temozolomide on U87MG and A172 Glioblastoma Cell Lines
Volume: 14
Issue: 2
Author(s): Georg Karpel-Massler, Mike-Andrew Westhoff, Richard E. Kast, Annika Dwucet, Lisa Nonnenmacher, C. Rainer Wirtz, Klaus-Michael Debatin and Marc-Eric Halatsch
Affiliation:
Keywords:
Artesunate, combination therapy, cytostasis, glioblastoma, necrosis, temozolomide.
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.
