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

Michaelis, M., Kleinschmidt, M. C., Barth, S., Rothweiler, F., Geiler, J., Breitling, R., Mayer, B., Deubzer, H., Witte, O., Kreuter, J., Doerr, H. W., Cinatl, J., Cinatl, J., Witt, O. & Cinatl Jr., J., 15-Jan-2010, In : Biochemical Pharmacology. 79, 2, p. 130-136 7 p.

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DOI

  • Martin Michaelis
  • Malte C. Kleinschmidt
  • Susanne Barth
  • Florian Rothweiler
  • Janina Geiler
  • Rainer Breitling
  • Bernd Mayer
  • Hedwig Deubzer
  • Olaf Witte
  • Joerg Kreuter
  • Hans Wilhelm Doerr
  • Jaroslav Cinatl
  • Jindrich Cinatl
  • Olaf Witt
  • Jindrich Cinatl Jr.

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-3(r)CDDP(1000) showed low sensitivity to artesunate. Characteristic gene expression signatures based on a previous analysis of artesunate resistance in the NC160 cell line panel clearly separated UKF-NB-3(r)CDDP(1000) from the other cell lines. L-Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate-cysteine ligase), resensitised in part UKF-NB-3(r)CDDP(1000) 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. (C) 2009 Elsevier Inc. All rights reserved.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalBiochemical Pharmacology
Volume79
Issue number2
Publication statusPublished - 15-Jan-2010

    Keywords

  • Neuroblastoma, Artesunate, Artemisinin, Chemoresistance, Cancer, Chemotherapy, GAMMA-GLUTAMYLCYSTEINE SYNTHETASE, TRADITIONAL CHINESE MEDICINE, AMINO-ACID-SEQUENCE, ASCITES TUMOR-CELLS, CYTOTOXIC ACTION, MULTIDRUG-RESISTANCE, EXPRESSION PROFILES, FALCIPARUM-MALARIA, OXIDATIVE STRESS, LEUKEMIA-CELLS

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