[Thiotert Induces Myelodysplastic Syndromes Cells Apoptosis by Activating Oxidative Stress]

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2024 Aug;32(4):1181-1185. doi: 10.19746/j.cnki.issn.1009-2137.2024.04.031.
[Article in Chinese]

Abstract

Objective: To explore whether thiotert treatment can inhibit proliferation and induce apoptosis in myelodysplastic syndromes (MDS) cells.

Methods: CCK-8 assay was used for determining the cytotoxicity of thiotert to MDS cell line SKM-1 and the reversal effect of GSH, NAC, and Z-VAD-FMK on thiotert-induced inhibition of cell viability. EdU assay was deployed to detect the cell proliferation ability. Intracellular reactive oxygen species (ROS) was measured by flow cytometry after DCFH-DA staining. The expression of DNA damage- and apoptosis-related proteins was detected by Western blot.

Results: Thiotert treatment significantly suppressed the cell viability and proliferation ability in SKM-1 cells. A large amount of ROS generation and markedly elevated C-PARP, C-Caspase 3, and γ-H2AX were observed after thiotert administration, while BCL-2 was significantly decreased. In addition, GSH, NAC, and Z-VAD-FMK were able to mitigate the cytotoxicity of thiotert on SKM-1 cells.

Conclusion: Thiotert can promote MDS cell apoptosis by mediating ROS production and pro-apoptotic proteins expression.

题目: 6-异丙基双硫-2′-脱氧鸟苷通过氧化应激诱导骨髓增生异常综合征细胞凋亡.

目的: 研究6-异丙基双硫-2′-脱氧鸟苷(thiotert)对骨髓增生异常综合征(MDS)细胞SKM-1增殖及凋亡的影响。.

方法: 采用CCK-8法检测thiotert对SKM-1细胞活力的抑制及GSH、NAC和Z-VAD-FMK对thiotert细胞毒性的逆转作用;EdU细胞增殖检测试剂盒检测细胞增殖情况;流式细胞术检测细胞内的活性氧(ROS)水平;Western blot检测DNA损伤及凋亡相关蛋白的表达。.

结果: thiotert显著抑制了SKM-1细胞的增殖能力,诱导SKM-1细胞中ROS水平升高;thiotert处理导致SKM-1细胞内C-PARP、C-Caspase 3和γ-H2AX蛋白表达上调,而BCL-2显著下调;抗氧化剂GSH和NAC及凋亡抑制剂Z-VAD-FMK能部分逆转thiotert对细胞活力的抑制作用。.

结论: thiotert能够通过介导ROS的产生和促凋亡蛋白的表达来促进MDS细胞发生凋亡。.

Keywords: myelodysplastic syndromes; thiotert; reactive oxygen species; apoptosis.

Publication types

  • English Abstract

MeSH terms

  • Apoptosis* / drug effects
  • Caspase 3 / metabolism
  • Cell Proliferation* / drug effects
  • Cell Survival / drug effects
  • DNA Damage
  • Humans
  • Myelodysplastic Syndromes* / metabolism
  • Oxidative Stress* / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species* / metabolism

Substances

  • Reactive Oxygen Species
  • Caspase 3
  • Proto-Oncogene Proteins c-bcl-2