Probenecid Sensitizes Neuroblastoma Cancer Stem Cells to Cisplatin

Abstract

We used both in vitro cultures of neuroblastoma cell lines and nude-mice xenotransplants to explore the effects of co-administration of cisplatin and probenecid. Probenecid sensitized neuroblastoma cells, including tumor cells with stem features, to the effects of cisplatin, both in vitro and in vivo. This effect was mediated by an increase in the apoptotic cell death and a concomitant decrease in cell proliferation. This effect is accompanied by modulation of the mRNA and protein of the drug efflux transporters MDR1, MRP2, and BCRP. The co-administration of probenecid with cisplatin should be explored as a possible therapeutic strategy.

Keywords:

• Chemotherapy
• Efficacy

Acknowledgements

The present work was supported by grants 87855 and 132931 by Consejo Nacional de Ciencia y Tecnologia to J. Melendez-Zajgla.

Declaration of interest

The authors report no conflicts of interest.