Proteomics explored the feasibility of curcumin as anticancer copper ionophore

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, 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 still lacks systematic analysis. Based on quantitative proteomics, we explored the feasibility of curcumin as anticancer copper ionophore. 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 discolored the suppression and acceleration of cuproptosis by GSH and curcumin, respectively. Our results are significative for understanding cuproptosis process and developing novel anticancer reagents based on cuproptosis.