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 ([Ca²⁺]_i). Furthermore, the elevation of [Ca²⁺]_i induced by clioquinol led to S‐phase cell cycle arrest. Similar to our previous studies, the increase in [Ca²⁺]_i 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.

中文翻译：

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Clioquinol以SERCA2依赖性方式抑制细胞生长

据报道，喹喔啉可以作为神经退行性疾病和癌症的潜在疗法。但是，其潜在机制尚不清楚。我们以前曾报道过，氯喹喹通过人类神经型SH-SY5Y细胞中钙水平的升高诱导S期细胞周期停滞。在这项研究中，观察到不同类型的细胞可以检测出氯碘喹对细胞内钙水平的影响是否是细胞类型特异性的。Cell Counting Kit-8分析表明，氯喹诺醇在不同细胞系中表现出不同程度的浓度依赖性细胞毒性，并且由其引起的生长抑制与细胞来源或致癌作用无关。此外，Clioquinol对细胞生长的抑制作用与其对细胞内钙含量（[Ca ²⁺]_我）。此外，由氯喹醇引起的[Ca ²⁺ ] _i升高导致S期细胞周期停滞。与我们以前的研究相似，[Ca ²⁺ ] _i的增加这归因于钙泵SERCA2表达水平的变化。细胞系之间SERCA2表达水平的比较表明，高水平SERCA2的细胞对氯喹醇更敏感。此外，使用UALCAN和人类蛋白质图谱进行的分析还显示，SERCA2在相应人体组织中的表达与本研究中测试的细胞相似，这表明在将来应用氯碘喹醇方面具有潜力。总之，我们的结果扩大了对氯喹醇分子机理的理解，并为合理使用氯喹醇提供了重要的策略。