Kilic Guven, Hacioglu Ceyhan, Tuncer Cengiz, Kar Ezgi, Kar Fatih, Taskesen Ahmet, Kurtulus Adem, Ipek Onder, Cetiner Oben Devin, Erdin Cigdem
Department of Neurosurgery, Düzce University, Faculty of Medicine, Düzce, Türkiye.
Department of Medical Biochemistry, Düzce University, Faculty of Medicine, Düzce, Türkiye.
J Cell Mol Med. 2025 Apr;29(7):e70529. doi: 10.1111/jcmm.70529.
Ferroptosis, a distinct form of regulated cell death, plays a role in glioma pathogenesis. SRY-box (SOX) transcription factors are key regulators of cancer progression. In this study, we investigated the role of SOX10 in ferroptosis induction in U87 cells following boric acid treatment. First, the cytotoxic effects of boric acid on HMC3 and U87 cells were assessed using CCK8 and BrdU incorporation assays. Subsequently, SOX10, GPX4, ACSL4, GSH, MDA, total ROS, Fe, and TFR levels were analysed using ELISA, Western blot, and RT-PCR techniques. Additionally, DAPI staining was performed to evaluate nuclear abnormalities. According to the CCK8 analysis, the IC50 value for boric acid was determined to be 3.12 mM for HMC3 cells and 532 μM for U87 cells, a finding further supported by BrdU incorporation analysis, which indicated that U87 cells were more sensitive to boric acid. Western blot and RT-PCR analyses revealed that SOX10 expression was significantly higher in U87 cells compared to HMC3 cells. Boric acid treatment led to a reduction in GSH, GPX4, and SOX10 levels in U87 cells, while inducing an increase in MDA, total ROS, ACSL4, Fe, and TFR levels. Moreover, microscopic analysis demonstrated that boric acid treatment induced both morphological and nuclear abnormalities in U87 cells. In conclusion, our findings demonstrate that SOX10 is involved in the ferroptosis signalling pathway and that boric acid effectively suppresses U87 cell viability by targeting the SOX10/GPX4/ACSL4 axis.
铁死亡是一种独特的程序性细胞死亡形式，在胶质瘤发病机制中起作用。SRY盒（SOX）转录因子是癌症进展的关键调节因子。在本研究中，我们调查了SOX10在硼酸处理后U87细胞铁死亡诱导中的作用。首先，使用CCK8和BrdU掺入试验评估硼酸对HMC3和U87细胞的细胞毒性作用。随后，使用ELISA、蛋白质免疫印迹和逆转录-聚合酶链反应技术分析SOX10、谷胱甘肽过氧化物酶4（GPX4）、长链脂酰辅酶A合成酶4（ACSL4）、谷胱甘肽（GSH）、丙二醛（MDA）、总活性氧（ROS）、铁（Fe）和转铁蛋白受体（TFR）水平。此外，进行4',6-二脒基-2-苯基吲哚（DAPI）染色以评估核异常。根据CCK8分析，确定硼酸对HMC3细胞的半数抑制浓度（IC50）值为3.12 mM，对U87细胞为532 μM，BrdU掺入分析进一步支持了这一发现，表明U87细胞对硼酸更敏感。蛋白质免疫印迹和逆转录-聚合酶链反应分析显示，与HMC3细胞相比，U87细胞中SOX10的表达显著更高。硼酸处理导致U87细胞中GSH、GPX4和SOX10水平降低，同时诱导MDA、总ROS、ACSL4、Fe和TFR水平升高。此外，显微镜分析表明，硼酸处理诱导U87细胞出现形态和核异常。总之，我们的研究结果表明，SOX10参与铁死亡信号通路，硼酸通过靶向SOX10/GPX4/ACSL4轴有效抑制U87细胞活力。
