Abstract:
The Cannabis sativa L. plant has been utilized as a natural herbal remedy for millennia and is the major source of phytocannabinoids. Although Lebanese cannabis has gained recognition for its recreational value and quality; its medicinal potential against blood cancers remains poorly understood. Previous studies have revealed that a Cannabis oil extract (COE) possesses anti-inflammatory and anticancer properties. In the current study, we aim to investigate the cancer-inhibitory properties of Lebanese COE on acute myeloid leukemia (AML) using WEHI-3 cell line and WEHI-3 induced AML BALB/c mice model. The chemical composition of COE was analyzed using GCMS. WEHI-3 cells were treated with increasing concentrations of COE to determine the IC50 after 24, 48 and 72-hours post treatment. Flow cytometry, ROS detection assay, and western blot analysis were used to identify the mechanism of action of COE on WEHI-3 cells. Results revealed that COE exhibited significant cytotoxicity against WEHI-3 cells with IC50 of 7.73 μg/mL, 4.23 μg/mL, and 4.03 μg/mL at 24, 48, and 72 hours respectively. Flow cytometry analysis showed that COE induces an apoptotic cell death in WEHI-3 cells. Western blots analysis further demonstrated that COE triggered a caspase-dependent apoptosis via the extrinsic and intrinsic pathways. In addition, COE significantly inhibited the MAPK pathway. A significant inhibition of ROS production was also observed with COE treatment. Animals treated with COE exhibited a higher survival rate and a significant reduction in spleen weight. In conclusion, COE exhibited a potent anti-cancer activity against AML cancer cells, both in vitro and in vivo, through a caspase-dependent apoptotic mechanism and MAPK pathway inhibition. These results call for more research to assess the potential use of COE as a chemotherapeutic agent in acute myeloid leukemia treatment.
