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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • University of Naples Federico II
  • University of Kent
  • Goethe University
  • SDN IRCCS
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Apoptosis, Chemoresistance, Epi-enprioline, Neuroblastoma, Vincristine
Original languageEnglish
Article number6577
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes