Kadriya Ahmad, Forbes-Robertson Sarah, Falah Mizied
Medical Research Institute, The Holy Family Hospital Nazareth, Nazareth 16100, Israel.
Azrieli Faculty of Medicine, Bar-Ilan University, Safed 1311502, Israel.
Molecules. 2024 Dec 18;29(24):5970. doi: 10.3390/molecules29245970.
Several cannabis plant-derived compounds, especially cannabinoids, exhibit therapeutic potential in numerous diseases and conditions. In particular, THC and CBD impart palliative, antiemetic, as well as anticancer effects. The antitumor effects include inhibition of cancerous cell growth and metastasis and induction of cell death, all mediated by cannabinoid interaction with the endocannabinoid system (ECS). However, the exact molecular mechanisms are still poorly understood. In addition, their effects on leukemia have scarcely been investigated. The current work aimed to assess the antileukemic effects of CBN and CBG on an acute monocytic leukemia cell line, the THP-1. THP-1 cell viability, morphology and cell cycle analyses were performed to determine potential cytotoxic, antiproliferative, and apoptotic effects of CBN and CBG. Western blotting was carried out to measure the expression of the proapoptotic p53. Both CBN and CBG inhibited cell growth and induced THP-1 cell apoptosis and cell cycle arrest in a dose- and time-dependent manner. CBN and CBG illustrated different dosage effects on THP-1 cells in the MTT assay (CBN > 40 μΜ, CBG > 1 μM) and flow cytometry (CBN > 5 μM, CBG > 40 μM), highlighting the cannabinoids' antileukemic activity. Our study hints at a direct correlation between p53 expression and CBG or CBN doses exceeding 50 μM, suggesting potential activation of p53-associated signaling pathways underlying these effects. Taken together, CBG and CBN exhibited suppressive, cell death-inducing effects on leukemia cells. However, further in-depth research will be needed to explore the molecular mechanisms driving the anticancer effects of CBN and CBG in the leukemia setting.
几种源自大麻植物的化合物，尤其是大麻素，在众多疾病和病症中展现出治疗潜力。特别是，四氢大麻酚（THC）和大麻二酚（CBD）具有缓解、止吐以及抗癌作用。其抗肿瘤作用包括抑制癌细胞生长和转移以及诱导细胞死亡，所有这些作用均由大麻素与内源性大麻素系统（ECS）相互作用介导。然而，确切的分子机制仍知之甚少。此外，它们对白血病的影响几乎未被研究。当前的研究旨在评估大麻酚（CBN）和大麻萜酚（CBG）对急性单核细胞白血病细胞系THP-1的抗白血病作用。进行了THP-1细胞活力、形态和细胞周期分析，以确定CBN和CBG潜在的细胞毒性、抗增殖和凋亡作用。通过蛋白质免疫印迹法检测促凋亡蛋白p53的表达。CBN和CBG均以剂量和时间依赖性方式抑制细胞生长并诱导THP-1细胞凋亡和细胞周期停滞。在MTT试验（CBN > 40 μΜ，CBG > 1 μM）和流式细胞术（CBN > 5 μM，CBG > 40 μM）中，CBN和CBG对THP-1细胞表现出不同的剂量效应，突出了大麻素的抗白血病活性。我们的研究表明，p53表达与超过50 μM的CBG或CBN剂量之间存在直接相关性，提示这些作用背后p53相关信号通路可能被激活。综上所述，CBG和CBN对白血病细胞具有抑制和诱导细胞死亡的作用。然而，需要进一步深入研究以探索在白血病环境中驱动CBN和CBG抗癌作用的分子机制。
