Department of Anatomy, Physiology, & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA; Shifa College of Dentistry, Shifa Tameer-e-Millat University, Islamabad, Pakistan.
Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
Life Sci. 2023 Aug 15;327:121862. doi: 10.1016/j.lfs.2023.121862. Epub 2023 Jun 15.
This study established the in vitro anti-lymphoma pharmacodynamic actions of the endocannabinoids (anandamide-AEA and 2-arachidonoylglycerol-2AG) on canine non-Hodgkin lymphoma (NHL) and human NHL cells.
The expression of cannabinoid (CB and CB) receptors in various canine NHL cells {1771, CLBL-1, CLL-1, peripheral blood mononuclear cells (PBMCs)} was studied using Quantitative real-time PCR (RT-qPCR). Anti-lymphoma cell viability assay was performed to assess the effect of endocannabinoids on various canine and human NHL cells (1771, CLBL-1, CLL-1, Ramos cells). The spectrophotometric and fluorometric procedures evaluated oxidative stress, inflammation, apoptosis, and mitochondrial function markers. SAS® and Prism-V La Jolla, CA, USA, were used for statistical analysis.
The current study validated the presence of CB and CB receptors in the canine NHL cells. There was a significantly higher expression of CB and CB receptors in B-cell lymphoma (BCL) cells (1771, CLBL-1, Ramos) compared to canine T-cell lymphoma (TCL) cells (CL-1). AEA and 2AG dose and time-dependently exhibited significant but differential anti-lymphoma effects on canine and human NHL cells. Anti-lymphoma pharmacodynamic actions of the endocannabinoids in the canine 1771 NHL cells revealed a significant alteration in the markers of oxidative stress, inflammation, and a decrease in mitochondrial function without altering the apoptotic markers.
Establishing the anti-lymphoma pharmacodynamic actions of endocannabinoids may provide new therapeutic interventions and expedite cannabinoid research.
本研究旨在确定大麻素内源性配体（大麻素受体激动剂）对犬非霍奇金淋巴瘤（NHL）和人 NHL 细胞的体外抗淋巴瘤药效作用。
采用实时定量 PCR（RT-qPCR）研究了各种犬 NHL 细胞（1771、CLBL-1、CLL-1、外周血单核细胞 [PBMC]）中大麻素（CB1 和 CB2）受体的表达。采用抗淋巴瘤细胞活力测定法评估大麻素内源性配体对各种犬和人 NHL 细胞（1771、CLBL-1、CLL-1、Ramos 细胞）的影响。采用分光光度法和荧光法评估氧化应激、炎症、凋亡和线粒体功能标志物。SAS 和 Prism-V（美国加利福尼亚州拉霍亚）用于统计分析。
本研究验证了犬 NHL 细胞中存在 CB1 和 CB2 受体。B 细胞淋巴瘤（BCL）细胞（1771、CLBL-1、Ramos）中 CB1 和 CB2 受体的表达明显高于 T 细胞淋巴瘤（TCL）细胞（CL-1）。AEA 和 2-AG 呈剂量和时间依赖性地对犬和人 NHL 细胞表现出显著但不同的抗淋巴瘤作用。大麻素内源性配体在犬 1771 NHL 细胞中的抗淋巴瘤药效作用导致氧化应激、炎症标志物显著改变，线粒体功能下降，而凋亡标志物无变化。
确定大麻素内源性配体的抗淋巴瘤药效作用可能为提供新的治疗干预措施，并加速大麻素研究。
