黎巴嫩大麻油作为急性髓性白血病的潜在治疗方法:体外和体内评估。
Lebanese Cannabis Oil as a Potential Treatment for Acute Myeloid Leukemia: In Vitro and In Vivo Evaluations.
发表日期:2024 Jul 02
作者:
Anthony Lteif, Wassim Shebaby, Marissa El Hage, Shirine Azar-Atallah, Dima Mroue, Mohamad Mroueh, Costantine F Daher
来源:
DIABETES & METABOLISM
摘要:
大麻 L. ssp。 indica (Lam.) 植物历史上一直被用作治疗多种疾病的天然草药。在黎巴嫩,大麻提取物长期以来一直被用于治疗关节炎、糖尿病和癌症。当前的研究旨在利用 WEHI-3 细胞研究黎巴嫩大麻油提取物 (COE) 对急性髓性白血病的抗癌特性,并利用WEHI-3诱导的白血病小鼠模型。用增加浓度的COE处理WEHI-3细胞,以确定处理后24、48和72小时后的IC50。利用流式细胞术来鉴定细胞死亡的模式。进行蛋白质印迹测定以评估凋亡标记蛋白。将WEHI-3细胞接种BALB/c小鼠建立体内模型,接种后10天开始治疗,持续3周。COE表现出显着的细胞毒性,IC50分别为7.76、3.82和3.34 μg/mL分别在治疗后24小时、48小时和72小时。 COE 治疗通过抑制 MAPK/ERK 途径诱导细胞凋亡,并通过独立于 ROS 产生的外在和内在模式触发 caspase 依赖性细胞凋亡。用 COE 治疗的动物表现出显着更高的存活率、脾脏重量以及白细胞计数的减少。COE 在体外和体内均表现出针对 AML 细胞的有效抗癌活性。这些发现强调了 COE 作为化疗辅助剂治疗急性髓系白血病的潜在应用。版权所有 © 2024。由 Elsevier B.V. 出版。
The Cannabis sativa L. ssp. indica (Lam.) plant has been historically utilized as a natural herbal remedy for the treatment of several ailments. In Lebanon, cannabis extracts have long been traditionally used to treat arthritis, diabetes, and cancer.The current study aims to investigate the anti-cancer properties of Lebanese cannabis oil extract (COE) on acute myeloid leukemia using WEHI-3 cells, and a WEHI-3-induced leukemia mouse model.WEHI-3 cells were treated with increasing concentrations of COE to determine the IC50 after 24, 48 and 72-h post treatment. Flow cytometry was utilized to identify the mode of cell death. Western blot assay was performed to assess apoptotic marker proteins. In vivo model was established by inoculating WEHI-3 cells in BALB/c mice, and treatment commencing 10 days post-inoculation and continued for a duration of 3 weeks.COE exhibited significant cytotoxicity with IC50 of 7.76, 3.82, and 3.34 μg/mL at 24, 48, and 72 h respectively post-treatment. COE treatment caused an induction of apoptosis through an inhibition of the MAPK/ERK pathway and triggering a caspase-dependent apoptosis via the extrinsic and intrinsic modes independent of ROS production. Animals treated with COE exhibited a significantly higher survival rate, reduction in spleen weight as well as white blood cells count.COE exhibited a potent anti-cancer activity against AML cells, both in vitro and in vivo. These findings emphasize the potential application of COE as a chemotherapeutic adjuvant in treatment of acute myeloid leukemia.Copyright © 2024. Published by Elsevier B.V.