Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines

Michaelis, M. et al. (2010) Anti-cancer effects of artesunate in a panel of chemoresistant neuroblastoma cell lines. Biochemical Pharmacology, 79(2), pp. 130-136. (doi: 10.1016/j.bcp.2009.08.013)

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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-3rCDDP1000 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-3rCDDP1000 from the other cell lines. l-Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate-cysteine ligase), resensitised in part UKF-NB-3rCDDP1000 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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Breitling, Professor Rainer
Authors: Michaelis, M., Kleinschmidt, M.C., Barth, S., Rothweiler, F., Geiler, J., Breitling, R., Mayer, B., Deubzer, H., Witt, O., Kreuter, J., Doerr, H.W., and Cinatl, J.
Subjects:Q Science > QH Natural history > QH345 Biochemistry
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Biochemical Pharmacology
ISSN:0006-2952
ISSN (Online):1873-2968
Published Online:19 August 2010

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