Abstract

In the recent years, the application of new antitumor drugs has focused on the replacement of conventional chemotherapeutics with compounds derived from natural products. Cannabidiol (CBD) is one of the 113 cannabinoids derived from the plant Cannabis sativa and is characterized with complex and not entirely understood biological function. Unlike the other most abundant cannabinoid in Cannabis sativa – tetrahydrocannabinol, cannabidiol has low affinity to the endocannabinoid receptors and the manifestation of its activity does not appear to rely on the endocannabinoid system. Cannabidiol is used in the treatment of many diseases including some types of cancer. The aim of our study was to evaluate the cytotoxic activity of cannabidiol and its effect on the process of programmed cell death. This process is directly involved in the antitumor effect of many drugs. Two lung cancer cell lines, A549 expressing р53 and H1299-p53 negative, were used. Apoptosis was monitored by Anexin V assay and the activation of Caspase 3/7. We found that CBD treatment led to a dose-dependant apoptosis increase in p53 positive A549 cells. The level of apoptosis in p53 negative H1299 cells was much lower and did not seem to be dose dependent. However, the total cell viability was similar for the two cell lines, which was due to the increased necrosis observed in H1299 cells.

摘要

近年来，新型抗肿瘤药物的应用主要集中在用天然产物衍生的化合物替代常规化疗药物。大麻二酚 (CBD) 是来自植物大麻的 113 种大麻素之一，具有复杂且尚未完全了解的生物学功能。与Cannabis sativa 中其他最丰富的大麻素不同– 四氢大麻酚，大麻二酚对内源性大麻素受体的亲和力低，其活性的表现似乎不依赖于内源性大麻素系统。大麻二酚用于治疗多种疾病，包括某些类型的癌症。我们研究的目的是评估大麻二酚的细胞毒活性及其对程序性细胞死亡过程的影响。这个过程直接参与了许多药物的抗肿瘤作用。使用了两种肺癌细胞系，表达 р53 的 A549 和阴性的 H1299-p53。通过 Anexin V 测定和半胱天冬酶 3/7 的激活监测细胞凋亡。我们发现 CBD 治疗导致 p53 阳性 A549 细胞的剂量依赖性细胞凋亡增加。p53 阴性 H1299 细胞的凋亡水平要低得多，而且似乎不依赖于剂量。然而，