Copper(ii) complex enhanced chemodynamic therapy through GSH depletion and autophagy flow blockade

Abstract

Three copper(II) complexes C1–C3 were synthesized and fully characterized as chemodynamic therapy (CDT) anticancer agents. C1–C3 showed greater cytotoxicity than their ligands toward SK-OV-3 and T24 cells. Particularly, C2 showed...

Copper in colorectal cancer: From copper‐related mechanisms to clinical cancer therapies

“… 31 , 37 Copper‐induced ROS also increase lipid peroxidation, deplete glutathione (GSH) and enhance cellular susceptibility to oxidative damage. 38 Moreover, copper accumulation in the cell nucleus damages DNA in various biological systems and inactivates sulphur‐containing enzymes by binding to their sulphur groups. 39 Additionally, copper ions inhibit the chymotrypsin‐like activity of the 20S proteasome and 19S proteasomal deubiquitinases, further inducing apoptosis.…”

“…This process leads to the release of cytochrome c and mitochondrial apoptosis‐inducing factor 1 into the cytoplasm, initiating caspase activation and DNA fragmentation 31,37 . Copper‐induced ROS also increase lipid peroxidation, deplete glutathione (GSH) and enhance cellular susceptibility to oxidative damage 38 . Moreover, copper accumulation in the cell nucleus damages DNA in various biological systems and inactivates sulphur‐containing enzymes by binding to their sulphur groups 39 .…”

Discovery of mitochondrion-targeting copper(ii)-plumbagin and -bipyridine complexes as chemodynamic therapy agents with enhanced antitumor activity

“…20 Cu( ii ) undergoes a redox reaction with GSH to generate oxidized glutathione (GSSG) and Cu( i ), which catalyzes the conversion of H 2 O 2 to ROS. 21–24 Moreover, copper complexes are less toxic than traditional platinum drugs. 25,26 Therefore, it is a promising strategy to use copper complexes to amplify ˙OH induced oxidative stress and reduce GSH to enhance the CDT effect.…”

Biomimetic Nanomedicine Targeting Orchestrated Metabolism Coupled with Regulatory Factors to Disrupt the Metabolic Plasticity of Breast Cancer

“…Some studies have shown that excessive oxidative stress can increase the membrane permeability of lysosomes and lead to lysosome dysfunction. 20 It also impairs the ability of the autophagolysosome to recycle nutrients. In addition, nanomedicines are often localized in lysosomes, and oxidative stress generated by nanomaterials may more effectively block autophagy flux at a later stage.…”

“…Various enzymes in the lysosome, such as protease, glycosidase, and phosphatase, complete the recovery of nutrients. Some studies have shown that excessive oxidative stress can increase the membrane permeability of lysosomes and lead to lysosome dysfunction . It also impairs the ability of the autophagolysosome to recycle nutrients.…”