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大麻二酚诱导人肺癌细胞和癌症干细胞死亡。

Cannabidiol Induces Cell Death in Human Lung Cancer Cells and Cancer Stem Cells.

作者信息

Hamad Hussein, Olsen Birgitte Brinkmann

机构信息

Department of Nuclear Medicine, Odense University Hospital, 5000 Odense C, Denmark.

Department of Clinical Research, University of Southern Denmark, 5000 Odense C, Denmark.

出版信息

Pharmaceuticals (Basel). 2021 Nov 17;14(11):1169. doi: 10.3390/ph14111169.

Abstract

Currently, there is no effective therapy against lung cancer due to the development of resistance. Resistance contributes to disease progression, recurrence, and mortality. The presence of so-called cancer stem cells could explain the ineffectiveness of conventional treatment, and the development of successful cancer treatment depends on the targeting also of cancer stem cells. Cannabidiol (CBD) is a cannabinoid with anti-tumor properties. However, the effects on cancer stem cells are not well understood. The effects of CBD were evaluated in spheres enriched in lung cancer stem cells and adherent lung cancer cells. We found that CBD decreased viability and induced cell death in both cell populations. Furthermore, we found that CBD activated the effector caspases 3/7, increased the expression of pro-apoptotic proteins, increased the levels of reactive oxygen species, as well as a leading to a loss of mitochondrial membrane potential in both populations. We also found that CBD decreased self-renewal, a hallmark of cancer stem cells. Overall, our results suggest that CBD is effective against the otherwise treatment-resistant cancer stem cells and joins a growing list of compounds effective against cancer stem cells. The effects and mechanisms of CBD in cancer stem cells should be further explored to find their Achilles heel.

摘要

目前,由于耐药性的产生,尚无针对肺癌的有效治疗方法。耐药性会导致疾病进展、复发和死亡。所谓癌症干细胞的存在可以解释传统治疗方法无效的原因,而成功的癌症治疗的发展也取决于对癌症干细胞的靶向作用。大麻二酚(CBD)是一种具有抗肿瘤特性的大麻素。然而,其对癌症干细胞的影响尚不清楚。我们评估了CBD对富含肺癌干细胞的球体和贴壁肺癌细胞的影响。我们发现CBD降低了这两种细胞群体的活力并诱导细胞死亡。此外,我们发现CBD激活了效应半胱天冬酶3/7,增加了促凋亡蛋白的表达,提高了活性氧水平,还导致这两种细胞群体的线粒体膜电位丧失。我们还发现CBD降低了自我更新能力,这是癌症干细胞的一个标志。总体而言,我们的结果表明CBD对原本耐药的癌症干细胞有效,并且加入了越来越多对癌症干细胞有效的化合物行列。应进一步探索CBD在癌症干细胞中的作用和机制,以找到它们的致命弱点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeef/8624994/63e4582cde84/pharmaceuticals-14-01169-g001.jpg

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