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.
Keywords: Artesunate, combination therapy, cytostasis, glioblastoma, necrosis, temozolomide.
Anti-Cancer Agents in Medicinal Chemistry
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.
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Karpel-Massler Georg, Westhoff Mike-Andrew, Kast E. Richard, Dwucet Annika, Nonnenmacher Lisa, Wirtz Rainer C., Debatin Klaus-Michael and Halatsch Marc-Eric, Artesunate Enhances the Antiproliferative Effect of Temozolomide on U87MG and A172 Glioblastoma Cell Lines, Anti-Cancer Agents in Medicinal Chemistry 2014; 14 (2) . https://dx.doi.org/10.2174/18715206113136660340
DOI https://dx.doi.org/10.2174/18715206113136660340 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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