Promising effects of the 4HPR-BSO combination in neuroblastoma monolayers and spheroids

Roos Cuperus, André B.P. Van Kuilenburg, René Leen, Johannes Bras, Huib N. Caron, Godelieve A.M. Tytgat

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

6 Citaten (Scopus)


To enhance the efficacy of fenretinide (4HPR)-induced reactive oxygen species (ROS) in neuroblastoma, 4HPR was combined with buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, in neuroblastoma cell lines and spheroids, the latter being a three-dimensional tumor model. 4HPR exposure (2.5-10 μM, 24 h) resulted in ROS induction (114-633%) and increased GSH levels (68-120%). A GSH depletion of 80% of basal levels was observed in the presence of BSO (25-100 μM, 24 h). The 4HPR-BSO combination resulted in slightly increased ROS levels (1.1- to 1.3-fold) accompanied by an increase in cytotoxicity (110-150%) compared to 4HPR treatment alone. A correlation was observed between the ROS-inducing capacity of each cell line and the increase in cytotoxicity induced by 4HPR-BSO compared to 4HPR. No significant correlation between baseline antioxidant levels and sensitivity to 4HPR or BSO was observed. In spheroids, 4HPR-BSO induced a strong synergistic growth retardation and induction of apoptosis. Our data show that BSO increased the cytotoxic effects of 4HPR in neuroblastoma monolayers and spheroids in ROS-producing cell lines. This indicates that the 4HPR-BSO combination might be a promising new strategy in the treatment of neuroblastoma.

Originele taal-2Engels
Pagina's (van-tot)1213-1220
Aantal pagina's8
TijdschriftFree Radical Biology and Medicine
Nummer van het tijdschrift6
StatusGepubliceerd - 15 sep. 2011
Extern gepubliceerdJa


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