Selenium-containing agents showed novel anticancer activity by triggering pro-oxidative mechanism. Studies confirmed that methylseleninic acid (MeSe) displayed broad-spectrum anti-tumor activity against kinds of human cancers. However, the anticancer effects and mechanism of MeSe against human glioma growth have not been explored yet. Herein, the present study showed that MeSeA dose-dependently inhibited U251 and U87 human glioma cells growth in vitro. Flow cytometry analysis indicated that MeSe induced significant U251 cells apoptosis with a dose-dependent manner, followed by the activation of caspase-7, caspase-9 and caspase-3. Immunofluorescence staining revealed that MeSe time-dependently caused reactive oxide species (ROS) accumulation and subsequently resulted in oxidative damage, as convinced by the increased phosphorylation level of Ser428-ATR, Ser1981-ATM, Ser15-p53 and Ser139-histone. ROS inhibition by glutathione (GSH) effectively attenuated MeSe-induced ROS generation, oxidative damage, caspase-3 activation and cytotoxicity, indicating that ROS was an upstream factor involved in MeSe-mediated anticancer mechanism in glioma. Importantly, MeSe administration in nude mice significantly inhibited glioma growth in vivo by inducing apoptosis through triggering oxidative damage. Taken together, our findings validated the possibility that MeSe as a selenium-containing can act as potential tumor chemotherapy agent for therapy of human glioma.

含硒制剂通过触发促氧化机制显示出新的抗癌活性。研究证实，甲基硒酸 (MeSe) 对多种人类癌症具有广谱抗肿瘤活性。然而，MeSe对人胶质瘤生长的抗癌作用和机制尚未被探索。在此，本研究表明 MeSeA 在体外剂量依赖性地抑制 U251 和 U87 人胶质瘤细胞的生长。流式细胞术分析表明，MeSe 以剂量依赖性方式诱导显着的 U251 细胞凋亡，随后激活 caspase-7、caspase-9 和 caspase-3。免疫荧光染色显示，MeSe 随时间变化引起活性氧化物 (ROS) 积累，并随后导致氧化损伤，Ser428-ATR、Ser1981-ATM、Ser15-p53 和 Ser139-组蛋白磷酸化水平的增加证实了这一点。谷胱甘肽 (GSH) 抑制 ROS 有效减弱 MeSe 诱导的 ROS 生成、氧化损伤、caspase-3 激活和细胞毒性，表明 ROS 是参与 MeSe 介导的胶质瘤抗癌机制的上游因素。重要的是，裸鼠体内施用 MeSe可通过触发氧化损伤诱导细胞凋亡，显着抑制体内神经胶质瘤的生长。综上所述，我们的研究结果证实了 MeSe 作为一种含硒化合物可以作为治疗人类神经胶质瘤的潜在肿瘤化疗药物。