"Proteomics revealed the crosstalk between copper stress and cuproptosis, and explored the feasibility of curcumin as anticancer copper ionophore"

作者全名："Yang, Ying; Liang, Shuyu; Geng, Hongen; Xiong, Mengmeng; Li, Man; Su, Qian; Jia, Fang; Zhao, Yimei; Wang, Kai; Jiang, Jun; Qin, Si; Li, Xiang"

作者地址："[Yang, Ying; Xiong, Mengmeng; Jia, Fang; Zhao, Yimei; Wang, Kai; Jiang, Jun; Li, Xiang] Hubei Univ, Coll Hlth Sci & Engn, Wuhan 430062, Hubei, Peoples R China; [Su, Qian; Qin, Si] Chongqing Med Univ, Affiliated Hosp 3, Dept Endocrinol, Chongqing 401120, Peoples R China; [Liang, Shuyu] Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China; [Geng, Hongen; Li, Man] Cent China Normal Univ, Sch Chem, Wuhan 430079, Hubei, Peoples R China; [Yang, Ying; Xiong, Mengmeng; Jia, Fang; Wang, Kai; Jiang, Jun; Li, Xiang] Hubei Univ, Hubei Prov Engn Ctr Performance Chem, Wuhan 430062, Hubei, Peoples R China"

通信作者："Zhao, YM; Li, X (通讯作者)，Hubei Univ, Coll Hlth Sci & Engn, Wuhan 430062, Hubei, Peoples R China.; Qin, S (通讯作者)，Chongqing Med Univ, Affiliated Hosp 3, Dept Endocrinol, Chongqing 401120, Peoples R China.; Li, X (通讯作者)，Hubei Univ, Hubei Prov Engn Ctr Performance Chem, Wuhan 430062, Hubei, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000897702000002

JCR分区：Q1

影响因子：7.4

年份：2022

卷号：193

期号：　

开始页：638

结束页：647

文献类型：Article

关键词：Copper stress; Cuproptosis; Quantitative proteomics; Curcumin; Glutathione

摘要："As an essential micronutrient element in organisms, copper controls a host of fundamental cellular functions. Recently, copper-dependent cell growth and proliferation have been defined as ""cuproplasia"". Conversely, ""cuproptosis"" represents copper-dependent cell death, in a nonapoptotic manner. So far, a series of copper ionophores have been developed to kill cancer cells. However, the biological response mechanism of copper uptake has not been systematically analyzed. Based on quantitative proteomics, we revealed the crosstalk be-tween copper stress and cuproptosis in cancer cells, and also explored the feasibility of curcumin as anticancer copper ionophore. Copper stress not only couples with cuproptosis, but also leads to reactive oxygen species (ROS) stress, oxidative damage and cell cycle arrest. In cancer cells, a feedback cytoprotection mechanism involving cuproptosis mediators was discovered. During copper treatment, the activation of glutamine trans-porters and the loss of Fe-S cluster proteins are the facilitators and results of cuproptosis, respectively. Through copper depletion, glutathione (GSH) blocks the cuproptosis process, rescues the activation of glutamine trans-porters, and prevents the loss of Fe-S cluster proteins, except for protecting cancer cells from apoptosis, protein degradation and oxidative damage. In addition, the copper ionophore curcumin can control the metabolisms of lipids, RNA, NADH and NADPH in colorectal cancer cells, and also up-regulates positive cuproptosis mediators. This work not only established the crosstalk between copper stress and cuproptosis, but also discolored the suppression and acceleration of cuproptosis by GSH and curcumin, respectively. Our results are significant for understanding cuproptosis process and developing novel anticancer reagents based on cuproptosis."

基金机构："College of Chemistry and Chemical Engineering, Hubei University; Third Affiliated Hospital of Chongqing Medical University [KY20075]"

基金资助正文："This work was supported by the start-up funding of College of Chemistry and Chemical Engineering, Hubei University; the ""Research Incubation Project"" of the Third Affiliated Hospital of Chongqing Medical University [KY20075]. We thank Prof. Yinxing Ni and Jian Zhong in the Third Affiliated Hospital of Chongqing Medical University for their help in the provision of Caco-2 cells."