文献类型：期刊文献

英文题名：Clioquinol inhibits cell growth in a SERCA2-dependent manner

作者：Lv, Xiaoguang[1];Zhang, Wei[1];Xia, Shengli[2];Huang, Zhiwei[3];Shi, Ping[1]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Shanghai Univ Med & Hlth Sci, Dept Orthoped, Affiliated Zhoupu Hosp, 1500 Zhoupu Zhouyuan Rd, Shanghai 201318, Peoples R China;[3]Donghua Univ, Coll Chem Chem Engn & Biotechnol, Key Lab Sci & Technol Ecotext, Minist Educ, Shanghai, Peoples R China

年份：2021

卷号：35

期号：5

外文期刊名：JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000612614100001)】；

基金：National Natural Science Foundation of China, Grant/Award Number: 31671309; the Training Planned Fund of Academic Leaders, Shanghai Pudong New Area Health System, Grant/Award Number: PWR 12018-09

语种：英文

外文关键词：[Ca2+](i); clioquinol; cytotoxicity; sensitivity; SERCA2

摘要：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.