Endocrine disrupting effects of marijuana and its mechanism

MCF-7人类乳腺癌细胞的增殖试验，E-SCREEN试验已经开发出来，利用雌激素对其靶细胞的增殖作用来评估化学物质的雌激素性。如果大麻和大麻素作为激动剂，那么它们应该模仿雌二醇对MCF-7细胞增殖反应的影响。本研究表明，在高达6.3□g/ml的剂量下，THCA菌株大麻提取物对MCF-7细胞的增殖具有剂量依赖性，而CBDA菌株则不像THCA菌株那样加速MCF-7细胞的增殖。然而，当剂量超过63□g/ml时，细胞生长明显受到抑制。推测高浓度提取物的抗增殖作用可能是由于其毒性或细胞凋亡所致。大麻素（THC、CBD和CBN）和THC代谢物在0.01 ~ 1000 nM的浓度范围内不存在浓度依赖效应。使用（ERE）3-Luc进行报告基因检测，大麻提取物和大麻烟提取物可刺激报告基因的转录活性。这些结果表明，在这个实验中使用的大麻素之外，大麻的一种可变成分是导致这种药物产生雌激素样作用的原因。例如，这可能是一种植物雌激素，它是大麻及其部分纯化成分的一种不稳定的污染物。

The proliferation assay of MCF-7 human breast cancer cells, E-SCREEN assay has been developed to assess the estrogenicity of chemicals using the proliferative effect of estrogens on their target cells. If marijuana and cannabinoids behave as agonists, then they should mimic the effects of estradiol on the proliferative response in MCF-7 cells. The present study demonstrated that at a dose of up to 6.3 □g/ml, extract of THCA strain marijuana stimulated the proliferation of MCF-7 cells in a dose-dependent manner, while that of CBDA strain did not accelerate such as the THCA strain. However, at a dose of more than 63 □g/ml, the cell growth was significantly inhibited. It was presumed that the anti-proliferative effect at the high concentration of Extract was due to toxicity or to apoptosis of cells. The cannabinoids (THC, CBD and CBN) and THC metabolites examined did not show concentration-dependent effects such as the extract at the concentration of 0.01 to 1000 nM. Marijuana extracts and marijuana smoke extracts stimulated transcriptional activity of reporter gene assay using (ERE)3-Luc. These results suggest that a variable component of marijuana other than cannabinoids used in this experiment is responsible for the estrogen-like effects of this drug. This could, for example, be a phytoestrogen that is an inconstant contaminant of marijuana and its partially purified components.