Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
Int J Mol Sci. 2023 Jan 18;24(3):1918. doi: 10.3390/ijms24031918.
Selenium is a promising multi-target chemotherapeutic agent with controversial clinical results. Hence, reassessing the anticancer effects of Se is necessary to clearly understand the potential of high-dose selenium in cancer treatment. Here, we observed that high-dose sodium selenite (SS) significantly decreased the proliferation and increased the death of ovarian cancer cells, mediated by an increased generation of reactive oxygen species. Notably, high-dose SS decreased the levels of glutathione peroxidase (GPx), a selenoprotein with antioxidant properties, without altering other selenoproteins. Furthermore, high-dose SS triggered lipid peroxidation and ferroptosis, a type of iron-dependent cell death, due to dysregulated GPx4 pathways. We demonstrated that intravenous high-dose SS significantly reduced the tumor growth and weight in SKOV3-bearing mice. Consistent with our in vitro results, mice with SKOV3 cells treated with high-dose SS showed decreased GPx4 expression in tumors. Therefore, we highlight the significance of high-dose SS as a potential chemotherapeutic agent for ovarian cancer. High-dose SS-mediated ferroptotic therapy integrating glutathione depletion and ROS generation is a promising strategy for cancer therapy.
硒是一种很有前途的多靶点化疗药物，但临床结果存在争议。因此，有必要重新评估硒的抗癌作用，以清楚了解高剂量硒在癌症治疗中的潜力。在这里，我们观察到高剂量亚硒酸钠（SS）通过增加活性氧的产生，显著降低卵巢癌细胞的增殖并增加其死亡。值得注意的是，高剂量 SS 降低了谷胱甘肽过氧化物酶（GPx）的水平，GPx 是一种具有抗氧化特性的硒蛋白，而其他硒蛋白则没有改变。此外，高剂量 SS 触发了脂质过氧化和铁死亡，这是一种依赖于铁的细胞死亡类型，这是由于 GPx4 途径失调所致。我们证明了静脉内高剂量 SS 可显著减少 SKOV3 荷瘤小鼠的肿瘤生长和体重。与我们的体外结果一致，用高剂量 SS 处理的 SKOV3 细胞的小鼠在肿瘤中显示出 GPx4 表达的降低。因此，我们强调了高剂量 SS 作为一种潜在的卵巢癌化疗药物的重要性。高剂量 SS 介导的铁死亡疗法整合了谷胱甘肽耗竭和 ROS 生成，是一种很有前途的癌症治疗策略。
