State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
Department of Orthopedics, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.
J Biochem Mol Toxicol. 2021 May;35(5):e22727. doi: 10.1002/jbt.22727. Epub 2021 Jan 28.
Clioquinol has been reported to act as a potential therapy for neurodegenerative diseases and cancer. However, the underlying mechanism is unclear. We have previously reported that clioquinol induces S-phase cell cycle arrest through the elevation of calcium levels in human neurotypic SH-SY5Y cells. In this study, different types of cells were observed to detect if the effect of clioquinol on intracellular calcium levels is cell type-specific. The Cell Counting Kit-8 assay showed that clioquinol exhibited varying degrees of concentration-dependent cytotoxicity in different cell lines, and that the growth inhibition caused by it was not related to cell source or carcinogenesis. In addition, the inhibition of cell growth by clioquinol was positively associated with its effect on intracellular calcium content ([Ca ] ). Furthermore, the elevation of [Ca ] induced by clioquinol led to S-phase cell cycle arrest. Similar to our previous studies, the increase in [Ca ] was attributed to changes in the expression levels of the calcium pump SERCA2. Comparison of expression levels of SERCA2 between cell lines showed that cells with high levels of SERCA2 were more sensitive to clioquinol. In addition, analysis using UALCAN and the Human Protein Atlas also showed that the expression of SERCA2 in the corresponding human tissues was similar to that of the cells tested in this study, suggesting potential in the application of clioquinol in the future. In summary, our results expand the understanding of the molecular mechanism of clioquinol and provide an important strategy for the rational use of clioquinol.
曲利秦已被报道可作为神经退行性疾病和癌症的潜在治疗药物。然而，其潜在机制尚不清楚。我们之前曾报道过，曲利秦通过提高人神经母细胞瘤 SH-SY5Y 细胞内的钙离子水平诱导 S 期细胞周期停滞。在这项研究中，观察了不同类型的细胞，以检测曲利秦对细胞内钙离子水平的影响是否具有细胞类型特异性。细胞计数试剂盒-8 检测表明，曲利秦在不同细胞系中表现出不同程度的浓度依赖性细胞毒性，其引起的生长抑制与细胞来源或癌变无关。此外，曲利秦对细胞生长的抑制与它对细胞内钙离子含量 ([Ca ]) 的影响呈正相关。此外，曲利秦引起的 [Ca ] 升高导致 S 期细胞周期停滞。与我们之前的研究类似，[Ca ] 的增加归因于钙泵 SERCA2 表达水平的变化。细胞系之间 SERCA2 表达水平的比较表明，SERCA2 水平较高的细胞对曲利秦更为敏感。此外，UALCAN 和人类蛋白质图谱的分析也表明，相应人组织中 SERCA2 的表达与本研究中测试的细胞相似，这表明曲利秦在未来具有潜在的应用价值。综上所述，我们的研究结果扩展了对曲利秦分子机制的理解，并为曲利秦的合理应用提供了重要策略。
