Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma

Wondossen Sime, Mohamed Jemaà, Yasmin Abassi, Vito Alessandro Lasorsa, Julie Bonne Køhler, Karin Hansson, Daniel Bexell, Martin Michaelis, Jindrich Cinatl, Daniel Strand, Mario Capasso, Ramin Massoumi

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

Sammanfattning

Neuroblastoma is a childhood solid tumour originating from undifferentiated neural progenitor cells of the sympathetic nervous system. Drug resistance of childhood cancer neuroblastoma is a serious clinical problem. In the present study, we aimed to identify novel drugs that can inhibit the growth and survival of chemoresistant neuroblastoma. High-throughput screening identified a small molecule, epi-enprioline that was able to induce apoptosis of vincristine-resistant neuroblastoma cells via the mitochondrial apoptotic pathway. Epi-enprioline reduced tumour growth in multiple preclinical models, including an orthotopic neuroblastoma patient-derived xenograft model in vivo. In summary, our data suggest that epi-enprioline can be considered as a lead compound for the treatment of vincristine-resistant neuroblastoma uncovering a novel strategy, which can be further explored as a treatment for drug-resistant neuroblastoma.

Originalspråkengelska
Artikelnummer6577
Antal sidor15
TidskriftInternational Journal of Molecular Sciences
Volym21
Nummer18
DOI
StatusPublished - 2020

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi

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