A Novel Highly Selective Cannabinoid CB2 Agonist Reduces in Vitro Growth and TGF-beta Release of Human Glial Cell Tumors.

Q3 Psychology

Central nervous system agents in medicinal chemistry Pub Date : 2019-11-30 DOI:10.2174/1871524919666190923154351

C. Cioni, M. Tassi, G. Marotta, C. Mugnaini, F. Corelli, P. Annunziata

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引用次数: 8

Abstract

BACKGROUND Cannabinoid receptors have been detected in human gliomas and cannabinoids have been proposed as novel drug candidates in the treatment of brain tumors. Aim of this study was to test the in vitro antitumor activity of COR167, a novel cannabinoid CB2-selective agonist displaying high binding affinity for human CB2 receptors, on tumor cells isolated from human glioblastoma multiforme and anaplastic astrocytoma. METHODS Glioma cell cultures were established from two glioblastoma multiforme and two anaplastic astrocytomas. Proliferation was measured in the presence or absence of COR167 with a bromodeoxyuridine (BrdU) cell proliferation ELISA assay. CB2 receptor expression was detected by western blotting. Apoptosis was assessed with phycoerythrin (PE) annexin V flow cytometry kit. TGF-beta 1 and 2 levels were analyzed in culture supernatants with commercial ELISAs. RESULTS COR167 was found to significantly reduce the proliferation of both glioblastoma and anaplastic astrocytoma in a dose-dependent manner at lower doses than other known, less specific CB2 agonists. This activity is independent of apoptosis and is associated with significant reduction of TGF-beta 1 and 2 levels in supernatants of glioma cell cultures. CONCLUSIONS These findings add to the role of cannabinoid CB2 receptor as a possible pharmacological target to counteract glial tumor growth and encourage further work to explore any other pharmacological effect of this novel CB2 agonist useful in the treatment of human gliomas.

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一种新型高选择性大麻素CB2激动剂减少人神经胶质细胞肿瘤的体外生长和tgf - β释放。

大麻素受体已经在人类胶质瘤中被检测到，大麻素已被提出作为治疗脑肿瘤的新候选药物。本研究的目的是检测一种新型大麻素CB2选择性激动剂COR167对人多形性胶质母细胞瘤和间变性星形细胞瘤分离的肿瘤细胞的体外抗肿瘤活性。方法分别从2例多形性胶质母细胞瘤和2例间变性星形细胞瘤中培养胶质瘤细胞。用溴脱氧尿苷(BrdU)细胞增殖ELISA法测定存在或不存在COR167时的增殖情况。western blotting检测CB2受体表达。细胞凋亡检测采用植红蛋白(PE)膜联蛋白V流式细胞术。用商业elisa分析培养上清中tgf - β 1和tgf - β 2的水平。结果发现，与其他已知的特异性较低的CB2激动剂相比，tscor167在较低剂量下以剂量依赖的方式显著降低胶质母细胞瘤和间变性星形细胞瘤的增殖。这种活性与细胞凋亡无关，与胶质瘤细胞培养上清中tgf - β 1和tgf - β 2水平的显著降低有关。结论这些发现增加了大麻素CB2受体作为抑制神经胶质瘤生长的可能药理靶点的作用，并鼓励进一步探索这种新型CB2激动剂在治疗人类神经胶质瘤中的任何其他药理作用。

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来源期刊

Central nervous system agents in medicinal chemistry Psychology-Neuropsychology and Physiological Psychology

CiteScore

2.10

自引率

0.00%

发文量

期刊介绍： Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.