Copper homeostasis and cuproptosis in tumor pathogenesis and therapeutic strategies

Abstract

Copper is an indispensable micronutrient for the development and replication of all eukaryotes, and its redox properties are both harmful and beneficial to cells. An imbalance in copper homeostasis is thought to be involved in carcinogenesis. Importantly, cancer cell proliferation, angiogenesis, and metastasis cannot be separated from the effects of copper. Cuproposis is a copper-dependent form of cell death that differs from other existing modalities of regulatory cell death. The role of cuproptosis in the pathogenesis of the nervous and cardiovascular systems has been widely studied; however, its impact on malignant tumors is yet to be fully understood from a clinical perspective. Exploring signaling pathways related to cuproptosis will undoubtedly provide a new perspective for the development of anti-tumor drugs in the future. Here, we systematically review the systemic and cellular metabolic processes of copper and the regulatory mechanisms of cuproptosis in cancer. In addition, we discuss the possibility of targeting copper ion drugs to prolong the survival of cancer patients, with an emphasis on the most representative copper ionophores and chelators. We suggest that attention should be paid to the potential value of copper in the treatment of specific cancers.

Cytotoxic Activity of the Red Grape Polyphenol Resveratrol against Human Prostate Cancer Cells: A Molecular Mechanism Mediated by Mobilization of Nuclear Copper and Generation of Reactive Oxygen Species

“…Usually, a sophisticated network involving the Snail repressor and the copper-dependent LOX-like proteins controls the transcription of E-cadherin. It has been observed that copper can influence the regulation of the epithelial-mesenchymal transition [40,49,50]. After discussing the crucial role of copper in cancer growth, it is important to emphasize that the elevated copper levels present in cancer can be specifically targeted to eliminate cancer cells.…”

Assessment of the Impact of Trace Essential Metals on Cancer Development

“…Ensuring a balance of copper ions in biological systems is crucial to preventing atherosclerosis and cardiovascular diseases associated with it [29]. Disruption in the regulation of copper levels is also believed to play a role in the process of carcinogenesis [30]. The concentrations of copper ions can function as a vital indicator of cancer progression [27].…”

“…Cuproptosis takes place when copper binds to lipoylated enzymes in the tricarboxylic acid (TCA) cycle, resulting in the aggregation of proteins, proteotoxic stress, and, ultimately, cancer cell death [42]. Nevertheless, the influence of cuproptosis on malignant tumours remains incompletely comprehended from a clinical standpoint [30]. In investigations concerning the anticancer efficacy of copper (II) complexes and other metallic coordination compounds on breast and lung cancer cells, the copper (II) complex displayed encouraging cytotoxic potency.…”

Comparative Transcriptome Analysis of the Hepatopancreas from Macrobrachium rosenbergii Exposed to the Heavy Metal Copper

“…On the one hand, Cu is an indispensable micronutrient for the development and homeostasis of all living organisms [1]. For example, it is an important cofactor of enzymes, including copper-zinc superoxide dismutase (SOD 1), cytochrome c oxidase (CCO), and lysyl oxidase (LOX) [2]. On the other hand, excessive Cu in the aquatic environment leads to the accumulation of reactive oxygen species (ROS) in aquatic organisms, leading to DNA damage, apoptosis, and tissue structure damage [3][4][5].…”