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

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Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma. / Sime, Wondossen; Jemaà, Mohamed; Abassi, Yasmin; Lasorsa, Vito Alessandro; Køhler, Julie Bonne; Hansson, Karin; Bexell, Daniel; Michaelis, Martin; Cinatl, Jindrich; Strand, Daniel; Capasso, Mario; Massoumi, Ramin.

I: International Journal of Molecular Sciences, Vol. 21, Nr. 18, 6577, 2020.

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Sime, Wondossen ; Jemaà, Mohamed ; Abassi, Yasmin ; Lasorsa, Vito Alessandro ; Køhler, Julie Bonne ; Hansson, Karin ; Bexell, Daniel ; Michaelis, Martin ; Cinatl, Jindrich ; Strand, Daniel ; Capasso, Mario ; Massoumi, Ramin. / Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma. I: International Journal of Molecular Sciences. 2020 ; Vol. 21, Nr. 18.

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TY - JOUR

T1 - Discovery of epi-enprioline as a novel drug for the treatment of vincristine resistant neuroblastoma

AU - Sime, Wondossen

AU - Jemaà, Mohamed

AU - Abassi, Yasmin

AU - Lasorsa, Vito Alessandro

AU - Køhler, Julie Bonne

AU - Hansson, Karin

AU - Bexell, Daniel

AU - Michaelis, Martin

AU - Cinatl, Jindrich

AU - Strand, Daniel

AU - Capasso, Mario

AU - Massoumi, Ramin

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Chemoresistance

KW - Epi-enprioline

KW - Neuroblastoma

KW - Vincristine

U2 - 10.3390/ijms21186577

DO - 10.3390/ijms21186577

M3 - Article

C2 - 32911859

AN - SCOPUS:85090630185

VL - 21

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1422-0067

IS - 18

M1 - 6577

ER -