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

Sime, Wondossen LU ; Jemaà, Mohamed LU ; Abassi, Yasmin LU ; Lasorsa, Vito Alessandro ; Køhler, Julie Bonne LU ; Hansson, Karin LU ; Bexell, Daniel LU ; Michaelis, Martin ; Cinatl, Jindrich and Strand, Daniel LU , et al. (2020) In International Journal of Molecular Sciences 21(18).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptosis, Chemoresistance, Epi-enprioline, Neuroblastoma, Vincristine
in
International Journal of Molecular Sciences
volume
21
issue
18
article number
6577
pages
15 pages
publisher
MDPI AG
external identifiers
  • pmid:32911859
  • scopus:85090630185
ISSN
1661-6596
DOI
10.3390/ijms21186577
language
English
LU publication?
yes
id
857cc6be-827f-4c12-86d0-bfdfcc4d9bdc
date added to LUP
2020-09-29 15:47:55
date last changed
2022-06-28 23:19:44
@article{857cc6be-827f-4c12-86d0-bfdfcc4d9bdc,
  abstract     = {{<p>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.</p>}},
  author       = {{Sime, Wondossen and Jemaà, Mohamed and Abassi, Yasmin and Lasorsa, Vito Alessandro and Køhler, Julie Bonne and Hansson, Karin and Bexell, Daniel and Michaelis, Martin and Cinatl, Jindrich and Strand, Daniel and Capasso, Mario and Massoumi, Ramin}},
  issn         = {{1661-6596}},
  keywords     = {{Apoptosis; Chemoresistance; Epi-enprioline; Neuroblastoma; Vincristine}},
  language     = {{eng}},
  number       = {{18}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma}},
  url          = {{http://dx.doi.org/10.3390/ijms21186577}},
  doi          = {{10.3390/ijms21186577}},
  volume       = {{21}},
  year         = {{2020}},
}