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提取液诱导人胰腺 3D 癌症模型细胞凋亡:其中主要抗氧化分子的重要性。

Extract Induces Apoptosis in Human Pancreatic 3D Cancer Models: Importance of Major Antioxidant Molecules Present Therein.

机构信息

IPHC, UMR 7178 CNRS, Faculté de Pharmacie, Université de Strasbourg, 67401 Illkirch, France.

Twistaroma, 300 Bd Sébastien Brant, 67412 Illkirch, France.

出版信息

Molecules. 2022 Feb 11;27(4):1214. doi: 10.3390/molecules27041214.

Abstract

In recent years, interest in L. has been rising, as legislation is moving in the right direction. This plant has been known and used for thousands of years for its many active ingredients that lead to various therapeutic effects (pain management, anti-inflammatory, antioxidant, etc.). In this report, our objective was to optimize a method for the extraction of cannabinoids from a clone of L. #138 resulting from an agronomic test (LaFleur, Angers, FR). Thus, we wished to identify compounds with anticancer activity on human pancreatic tumor cell lines. Three static maceration procedures, with different extraction parameters, were compared based on their median inhibitory concentration (IC) values and cannabinoid extraction yield. As CBD emerged as the molecule responsible for inducing apoptosis in the human pancreatic cancer cell line, a CBD-rich cannabis strain remains attractive for therapeutic applications. Additionally, while gemcitabine, a gold standard drug in the treatment of pancreatic cancer, only triggers cell cycle arrest in G0/G1, CBD also activates the cell signaling cascade to lead to programmed cell death. Our results emphasize the potential of natural products issued from medicinal hemp for pancreatic cancer therapy, as they lead to an accumulation of intracellular superoxide ions, affect the mitochondrial membrane potential, induce G1 cell cycle arrest, and ultimately drive the pancreatic cancer cell to lethal apoptosis.

摘要

近年来,随着立法的方向正确,人们对大麻素的兴趣日益浓厚。这种植物因其具有多种活性成分而闻名于世,这些成分具有各种治疗效果(如止痛、抗炎、抗氧化等)。在本报告中,我们的目的是优化一种从农业测试(LaFleur,昂热,FR)克隆的大麻素 #138 中提取大麻素的方法。因此,我们希望鉴定出对人胰腺肿瘤细胞系具有抗癌活性的化合物。我们比较了三种不同提取参数的静态浸提方法,其依据是它们的半数抑制浓度 (IC) 值和大麻素提取率。由于 CBD 是诱导人胰腺癌细胞系凋亡的分子,因此富含 CBD 的大麻品种仍然具有吸引力,可用于治疗应用。此外,虽然吉西他滨是治疗胰腺癌的金标准药物,仅能触发 G0/G1 细胞周期停滞,但 CBD 也能激活细胞信号级联反应,导致程序性细胞死亡。我们的结果强调了药用大麻衍生的天然产物在胰腺癌治疗中的潜力,因为它们导致细胞内超氧阴离子的积累,影响线粒体膜电位,诱导 G1 细胞周期停滞,并最终导致胰腺癌细胞发生致命的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2845/8880463/b4221bfac391/molecules-27-01214-g001.jpg

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