Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand.
Laboratory of Cell-Based Assays and Innovations, School of Biotechnology, Institute of Agricultural Technology, Suranaree University of Technology, 111 University Avenue, Nakhon Ratchasima 30000, Thailand.
Toxicol In Vitro. 2018 Feb;46:113-121. doi: 10.1016/j.tiv.2017.10.002. Epub 2017 Oct 4.
Brain cancer, in particular neuroblastoma and glioblastoma, is a global challenge to human health. Cordycepin, extracted from Cordyceps ssp., has been revealed as a strong anticancer agent through several ways; however, the mechanism, by which cordycepin counteracts brain cancers, is still poorly understood. In this study, the underlying mechanisms of cordycepin against human brain cancer cells were explored. SH-SY5Y and U251 cells were being a model to represent human neuroblastoma and glioblastoma, respectively. Here, it was found that cordycepin inhibited cell growth, and induced apoptosis in a dose-dependent manner in both SH-SY5Y and U-251 cell lines. The expression of pro-apoptotic genes, including P53, BAX, Caspase-3, and Caspase-9, were upregulated, whereas the expression of anti-apoptotic gene, BCL-2, was suppressed. Besides, cordycepin induced the generation of reactive oxygen species (ROS) along with the suppression of antioxidant genes, including GPX, SOD, and Catalase. Importantly, cordycepin was shown to involve in the activation of autophagy, which was evidenced by the increment of LC3I/II. The combination of cordycepin with chloroquine, an autophagy inhibitor, further inhibited the growth, and enhanced the death of brain cancer cells. Altogether, this finding suggested that cordycepin induced apoptosis of human brain cancer cells through mitochondrial-mediated intrinsic pathway and the modulation of autophagy. Therefore, cordycepin could be a promising candidate for the development of anticancer drugs targeting human brain cancers.
脑癌，特别是神经母细胞瘤和胶质母细胞瘤，是全球人类健康面临的一个挑战。从虫草中提取的虫草素已被证实是一种通过多种途径具有强大抗癌作用的物质；然而，虫草素对抗脑癌的机制仍知之甚少。在本研究中，探索了虫草素对抗人脑癌细胞的潜在机制。SH-SY5Y 和 U251 细胞分别作为神经母细胞瘤和胶质母细胞瘤的模型。结果发现，虫草素以剂量依赖的方式抑制 SH-SY5Y 和 U-251 细胞系的细胞生长并诱导细胞凋亡。促凋亡基因（包括 P53、BAX、Caspase-3 和 Caspase-9）的表达上调，而抗凋亡基因 BCL-2 的表达受到抑制。此外，虫草素诱导活性氧（ROS）的产生，同时抑制抗氧化基因（包括 GPX、SOD 和 Catalase）的表达。重要的是，虫草素被证明参与了自噬的激活，这可以通过 LC3I/II 的增加来证明。虫草素与自噬抑制剂氯喹联合使用进一步抑制了脑癌细胞的生长并增强了其死亡。总之，这些发现表明虫草素通过线粒体介导的内在途径和自噬的调节诱导人脑癌细胞凋亡。因此，虫草素可能是开发针对人脑癌的抗癌药物的有前途的候选药物。
