Department of Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang 550025, China.
Key Laboratory of Human Brain Bank for Functions and Diseases, Guizhou Medical University, Guiyang 550025, China.
Molecules. 2023 Dec 13;28(24):8062. doi: 10.3390/molecules28248062.
Gastrodin, the primary bioactive compound found in Gastrodia elata, has been shown to exhibit neuroprotective properties in a range of neurological disorders. However, the precise mechanisms through which gastrodin influences glioma cells remain unclear, and there is a scarcity of data regarding its specific effects. To ascertain the viability of glioma cell lines LN229, U251, and T98, the CCK-8 assay, a colony formation assay, and a 3D culture model were employed, utilizing varying concentrations of gastrodin (0, 5, 10, and 20 μM). Gastrodin exhibited a notable inhibitory effect on the growth of glioma cells, as evidenced by its ability to suppress colony formation and spheroid formation. Additionally, gastrodin induced ferroptosis in glioma cells, as it can increase the levels of reactive oxygen species (ROS) and peroxidized lipids, and reduced the levels of glutathione. Using a subcutaneous tumor model, gastrodin was found to significantly inhibit the growth of the T98 glioma cell line in vivo. Using high-throughput sequencing, PPI analysis, and RT-qPCR, we successfully identified Homeobox D10 (HOXD10) as the principal target of gastrodin. Gastrodin administration significantly enhanced the expression of HOXD10 in glioma cells. Furthermore, treatment with gastrodin facilitated the transcription of ACSL4 via HOXD10. Notably, the inhibition of HOXD10 expression impeded ferroptosis in the cells, which was subsequently restored upon rescue with gastrodin treatment. Overall, our findings suggest that gastrodin acts as an anti-cancer agent by inducing ferroptosis and inhibiting cell proliferation in HOXD10/ACSL4-dependent pathways. As a prospective treatment for gliomas, gastrodin will hopefully be effective.
天麻中的主要生物活性化合物天麻素已被证明在多种神经退行性疾病中具有神经保护作用。然而，天麻素影响神经胶质瘤细胞的确切机制尚不清楚，关于其具体作用的数据也很少。为了确定 LN229、U251 和 T98 神经胶质瘤细胞系的活力，采用 CCK-8 检测、集落形成检测和 3D 培养模型，使用不同浓度的天麻素（0、5、10 和 20 μM）。天麻素对神经胶质瘤细胞的生长表现出显著的抑制作用，表现为抑制集落形成和球体形成的能力。此外，天麻素诱导神经胶质瘤细胞发生铁死亡，因为它可以增加活性氧（ROS）和过氧化脂质的水平，降低谷胱甘肽的水平。在皮下肿瘤模型中，发现天麻素在体内显著抑制 T98 神经胶质瘤细胞系的生长。通过高通量测序、PPI 分析和 RT-qPCR，我们成功地确定了同源盒蛋白 D10（HOXD10）是天麻素的主要靶点。天麻素给药显著增强了神经胶质瘤细胞中 HOXD10 的表达。此外，天麻素处理通过 HOXD10 促进 ACSL4 的转录。值得注意的是，HOXD10 表达的抑制阻碍了细胞中的铁死亡，随后用天麻素处理恢复了铁死亡。总的来说，我们的研究结果表明，天麻素通过诱导铁死亡和 HOXD10/ACSL4 依赖性途径抑制细胞增殖来发挥抗癌作用。作为一种潜在的治疗神经胶质瘤的方法，天麻素有望发挥作用。
