Department of Neurosurgery, Jiangyin People's Hospital Affiliated to Nantong University, Jiangyin, Wuxi, China.
Department of Central Laboratory, Jiangyin People's Hospital Affiliated to Nantong University, Jiangyin, Wuxi, China.
Anat Rec (Hoboken). 2020 Aug;303(8):2192-2201. doi: 10.1002/ar.24242. Epub 2019 Sep 29.
Glioblastoma multiforme (GBM, WHO grade IV astrocytoma) has become a public health burden worldwide. Alpinumisoflavone (AIF) is a flavonoid compound isolated from Derris eriocarpa. This study aims to examine the role of AIF in GBM. Our results showed that AIF could decrease the cell viability of both T98G and U373 GBM cell lines. AIF treatment also caused cell cycle arrest at G1/G0 phase along with upregulation of p27 and downregulation of cyclin D1. AIF could significantly induce apoptosis in GBM cells. Activation of caspase-9, disruption of mitochondrial membrane potential and loss of mitochondrial cytochrome C were also observed following AIF treatment. Inhibition of glycolysis by AIF was demonstrated by reducing glucose consumption and lactate output in GBM cells. Moreover, HK2 was identified as the molecular target responsible for the anticancer activities of AIF against GBM cells. The results showed that HK2 knockdown enhanced the anticancer activities of AIF whereas ectopic HK2 expression compromised its effect. Furthermore, the antineoplastic activities of AIF in vivo were also validated in xenograft murine model. Our results showed that AIF can exhibit anticancer activities in GBM by promoting apoptosis and inhibiting glycolysis via targeting HK2.
多形性胶质母细胞瘤（GBM，WHO 分级 IV 星形细胞瘤）已成为全球公共卫生负担。琴叶榕素（AIF）是从鱼藤中分离得到的一种黄酮类化合物。本研究旨在探讨 AIF 在 GBM 中的作用。我们的研究结果表明，AIF 可降低 T98G 和 U373 GBM 细胞系的细胞活力。AIF 处理还导致细胞周期停滞在 G1/G0 期，同时上调 p27 和下调细胞周期蛋白 D1。AIF 可显著诱导 GBM 细胞凋亡。AIF 处理后还观察到 caspase-9 的激活、线粒体膜电位的破坏和线粒体细胞色素 C 的丢失。通过减少 GBM 细胞中葡萄糖的消耗和乳酸的产生，证实了 AIF 对糖酵解的抑制作用。此外，还鉴定出 HK2 是 AIF 对 GBM 细胞发挥抗癌活性的分子靶标。结果表明，HK2 敲低增强了 AIF 的抗癌活性，而外源性 HK2 表达则削弱了其作用。此外，AIF 在体内的抗肿瘤活性也在异种移植小鼠模型中得到了验证。我们的研究结果表明，AIF 通过靶向 HK2 促进凋亡和抑制糖酵解，在 GBM 中表现出抗癌活性。
