Cannabinoids induce cell death in leukaemic cells through Parthanatos and PARP-related metabolic disruptions.

ABSTRACT:

Background

Several studies have described a potential anti-tumour effect of cannabinoids (CNB). CNB receptor 2 (CB2) is mostly present in hematopoietic stem cells (HSC). The present study evaluates the anti-leukaemic effect of CNB.

Methods

Cell lines and primary cells from acute myeloid leukaemia (AML) patients were used and the effect of the CNB derivative WIN-55 was evaluated in vitro, ex vivo and in vivo.

Results

We demonstrate a potent antileukemic effect of WIN-55 which is abolished with CB antagonists. WIN-treated mice, xenografted with AML cells, had better survival as compared to vehicle or cytarabine. DNA damage-related genes were affected upon exposure to WIN. Co-incubation with the PARP inhibitor Olaparib prevented WIN-induced cell death, suggesting PARP-me

SUBMITTER: Medrano M 

PROVIDER: S-EPMC11058274 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature