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  • 1
    Language: English
    In: Biochemical Pharmacology, 15 January 2010, Vol.79(2), pp.130-136
    Description: 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 CDDP 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-3 CDDP from the other cell lines. -Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate–cysteine ligase), resensitised in part UKF-NB-3 CDDP 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.
    Keywords: Neuroblastoma ; Artesunate ; Artemisinin ; Chemoresistance ; Cancer ; Chemotherapy ; Pharmacy, Therapeutics, & Pharmacology ; Chemistry
    ISSN: 0006-2952
    E-ISSN: 1873-2968
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  • 2
    Language: English
    In: International journal of oncology, February 2006, Vol.28(2), pp.439-46
    Description: The proteasome inhibitor bortezomib (Velcade) was recently approved for the treatment of therapy-refractive multiple myeloma and is under investigation for numerous other types of cancer. A phase I clinical trial in paediatric patients resulted in tolerable toxicity. Since the emergence of chemoresistance represents one of the major drawbacks in cancer therapy, we investigated the influence of bortezomib on multi-drug resistant human neuroblastoma cell lines characterised by P-glycoprotein expression and p53 mutation. Nanomolar concentrations of bortezomib inhibited the cell cycle and induced apoptosis in chemosensitive as well as in chemoresistant cell lines. In vivo growth of chemosensitive and chemoresistant neuroblastoma cell lines was inhibited to a similar extent. In addition, bortezomib inhibited vessel formation in neuroblastoma xenografts. These findings and the favourable toxicity profile of bortezomib in children make it reasonable to further pursue additional development of the drug for the treatment of neuroblastoma and other paediatric solid tumours.
    Keywords: Antineoplastic Agents -- Pharmacology ; Boronic Acids -- Pharmacology ; Neuroblastoma -- Prevention & Control ; Pyrazines -- Pharmacology
    ISSN: 1019-6439
    E-ISSN: 17912423
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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