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©The Author(s) 2023.
World J Clin Oncol. Sep 24, 2023; 14(9): 324-334
Published online Sep 24, 2023. doi: 10.5306/wjco.v14.i9.324
Published online Sep 24, 2023. doi: 10.5306/wjco.v14.i9.324
Figure 1 Effects of excess copper and copper deficiency in cancer.
Four copper-related pathways with cancer inhibition effects are described. Elesclomol mediates the entry of Cu2+ into the mitochondria and causes reactive oxygen species accumulation. Flavonoids interfere with copper ion oxidation and reduction, inducing mitochondrial apoptosis pathway activation. Copper diethyldithiocarbamate can inhibit proteasome and result in endoplasmic reticulum stress. Copper deficiency can suppress the proliferation and migration of endothelial cells and the formation of connexin, bridling tumor angiogenesis. TCA: Tricarboxylic acid; ROS: Reactive oxygen species; FDX1: Ferredoxin 1; MTF1: Metallothionein; CTR1: Consolidation tumor ratio-1.
Figure 2 General molecular biological process of cuproptosis.
Copper can be transported into cells through the action of consolidation tumor ratio-1 and elesclomol encapsulation. When Cu2+ encapsulated by elesclomol enter the mitochondria, it gains an electron from ferrodoxin 1 (FDX1) (FDX1 expression can be promoted by metallothionein) and converts into Cu+. Concurrently, proteins responsible for dehydrogenation and acyl transfer (dihydrolipoamide transacetylase, dihydrolipoamide S-succinyltransferase, dihydrolipoamide dehydrogenase, pyruvate dehydrogenase α1, and pyruvate dehydrogenase β) undergo electron loss and are liporated by lipoic acid synthase. Subsequently, Cu+ promotes the oligomerization of liporated proteins. This cascade of events leads to a series of phenomena, including reactive oxygen species accumulation, mitochondrial dysfunction, and tricarboxylic acid inhibition, ultimately culminating in cuproptosis. CTR1: Consolidation tumor ratio-1; (Cu (DDC)2): Copper diethyldithiocarbamate; FDX1: Ferrodoxin 1.
Figure 3 The mechanisms underlying cuproptosis in cancer cells.
GSH: Glutathione.
- Citation: Wang J, Luo LZ, Liang DM, Guo C, Huang ZH, Sun GY, Wen J. Progress in the research of cuproptosis and possible targets for cancer therapy. World J Clin Oncol 2023; 14(9): 324-334
- URL: https://www.wjgnet.com/2218-4333/full/v14/i9/324.htm
- DOI: https://dx.doi.org/10.5306/wjco.v14.i9.324