Park Yoon-Jong, Na Han-Heom, Kwon In-Seo, Hwang Yu-Na, Park Hye-Jin, Kwon Tae-Hyung, Park Jin-Sung, Kim Keun-Cheol
Department of Biological Sciences, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
Kangwon Center for System Imaging, Kangwon National University, Chuncheon 24341, Korea.
Pharmaceuticals (Basel). 2022 Jul 6;15(7):836. doi: 10.3390/ph15070836.
Extracts of phytocannabinoids from have been studied for therapeutic purposes. Although nonpsychoactive CBD has been studied as a promising anticancer drug because it induces apoptosis in many cancer cells, it is also known to induce several physiological changes. In this study, we clarify the functional role it plays in the morphological characteristics of intracellular vesicle formation as well as apoptosis in A549 human lung cancer cells. CBD treatment shows growth inhibition at concentrations above 20 μM, but FACS analysis shows low efficacy in terms of cell death. Microscopic observations suggest that multiple vesicles were detected in the cytoplasmic region of CBD-treated A549 cells. CBD treatment upregulates apoptosis-related proteins, such as p53, PARP, RIP1, RIP3, Atg12, and Beclin, indicating that CBD regulates several types of cell death. CBD treatment also induced E-cadherin, PPARγ, clathrin, β-adaptin, and Tsg101, also known to be cellular-differentiation inducers or vesicle-formation components. Treatment combining CBD with GW9662, a PPARγ inhibitor, reduced CBD-induced cytoplasmic vesicle formation. This indicates that PPARγ regulates the vesicle-formation mechanism. However, CBD-treated E-cad KO clones did not show this regulatory mechanism. These results elucidate the pharmacological and molecular networks associated with CBD in PPARγ-dependent vesicle formation and the induction of apoptosis.
来自[具体来源未提及]的植物大麻素提取物已被用于治疗目的的研究。尽管非精神活性的大麻二酚（CBD）作为一种有前景的抗癌药物已被研究，因为它能诱导许多癌细胞凋亡，但它也会引起一些生理变化。在本研究中，我们阐明了它在A549人肺癌细胞内囊泡形成的形态特征以及凋亡中所起的功能作用。CBD处理在浓度高于20μM时显示出生长抑制作用，但流式细胞术分析表明在细胞死亡方面效果不佳。显微镜观察表明，在经CBD处理的A549细胞的细胞质区域检测到多个囊泡。CBD处理上调了凋亡相关蛋白，如p53、聚（ADP - 核糖）聚合酶（PARP）、受体相互作用蛋白1（RIP1）、受体相互作用蛋白3（RIP3）、自噬相关蛋白12（Atg12）和Beclin，表明CBD调节多种类型的细胞死亡。CBD处理还诱导了E - 钙黏蛋白、过氧化物酶体增殖物激活受体γ（PPARγ）、网格蛋白、β - 衔接蛋白和肿瘤易感基因101（Tsg101），这些蛋白也被认为是细胞分化诱导剂或囊泡形成成分。将CBD与PPARγ抑制剂GW9662联合处理可减少CBD诱导的细胞质囊泡形成。这表明PPARγ调节囊泡形成机制。然而，经CBD处理的E - 钙黏蛋白基因敲除克隆并未显示出这种调节机制。这些结果阐明了与CBD在PPARγ依赖性囊泡形成和凋亡诱导中相关的药理和分子网络。
