Targeting copper metabolism: a promising strategy for cancer treatment

Kong, Rong; Sun, Guojuan

doi:10.3389/fphar.2023.1203447

“…Notably, smoking, which is a major risk factor, contributes to the formation of malignant lung tissue [90]. In NSCLC, excessive copper accumulation within cancer cells has been closely linked with tumor growth and metastasis [91]. Disrupting copper homeostasis with copper-binding agents like disulfiram has shown promise by enhancing the efficacy of chemotherapy drugs, such as cisplatin, through the induction of oxidative stress and inhibition of DNA mechanisms in lung cancer cells [92].…”

Section: Non-small Cell Lung Cancermentioning

confidence: 99%

Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Springer,

Humayun,

Skouta

2024

Cancers

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Copper, an essential element for various biological processes, demands precise regulation to avert detrimental health effects and potential cell toxicity. This paper explores the mechanisms of copper-induced cell death, known as cuproptosis, and its potential health and disease implications, including cancer therapy. Copper ionophores, such as elesclomol and disulfiram, increase intracellular copper levels. This elevation triggers oxidative stress and subsequent cell death, offering potential implications in cancer therapy. Additionally, copper ionophores disrupt mitochondrial respiration and protein lipoylation, further contributing to copper toxicity and cell death. Potential targets and biomarkers are identified, as copper can be targeted to those proteins to trigger cuproptosis. The role of copper in different cancers is discussed to understand targeted cancer therapies using copper nanomaterials, copper ionophores, and copper chelators. Furthermore, the role of copper is explored through diseases such as Wilson and Menkes disease to understand the physiological mechanisms of copper. Exploring cuproptosis presents an opportunity to improve treatments for copper-related disorders and various cancers, with the potential to bring significant advancements to modern medicine.

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“…In addition to the genetic disorders described above, Cu dyshomeostasis has been associated with a large number of diseases, namely neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases, and amyotrophic lateral sclerosis [67,68], as well as atherosclerosis [69], diabetes mellitus [70], and cancer [10,71,72]. Recent studies have demonstrated a strong correlation between Cu and three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis [71,72]. Cu also has a role in oxidative stress and chronic inflammation, which promote cell transformation [35,73].…”

Section: Copper and Pathogenesismentioning

confidence: 99%

“…The recognition that Cu can have a crucial role in disease pathogenesis has led to the development of therapeutic strategies designed to modulate Cu transport and concentrations; to date, the main focus has been on strategies to treat different types of cancer [72,212,213]. Currently, there is significant interest in strategies to mitigate Cu dyshomeostasis, and hence, the attractiveness of applying these therapeutic strategies to the gynecological diseases analyzed in this review.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Copper in Gynecological Diseases

Conforti,

Delsouc,

Zorychta

et al. 2023

IJMS

8

0

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Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes’ and Wilson’s diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

show abstract

“…In addition to the genetic disorders described above, Cu dyshomeostasis has been associated with a large number of diseases: neurodegenerative disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases, and amyotrophic lateral sclerosis [67,68], as well as atherosclerosis [69], diabetes mellitus [70], and cancer [10,71,72]. Recent studies have demonstrated a strong correlation between Cu and three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis [71,72]. Cu also has a role in oxidative stress and chronic inflammation, which promote cell transformation [35,73].…”

Section: Copper and Pathogenesismentioning

confidence: 99%

“…The recognition that Cu can have a crucial role in disease pathogenesis has led to the development of therapeutic strategies designed to modulate Cu transport and concentrations; to date, the main focus has been on strategies to treat different types of cancer [72,205,206]. Currently, there is significant interest in strategies to mitigate Cu dyshomeostasis; hence, the attractiveness of applying these therapeutic strategies to the gynecological diseases analyzed in this review.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Copper in Gynecological Diseases

Conforti,

Delsouc,

Zorychta

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Copper (Cu) is an essential micronutrient for the correct development of eukaryotic organisms. This metal plays a key role in many cellular and physiological activities, including enzymatic activity, oxygen transport, and cell signaling. Although the redox activity of Cu is crucial for enzymatic reactions, this property also makes it potentially toxic when found at high levels. Due to this dual action of Cu, highly regulated mechanisms are necessary to prevent both the deficiency and the accumulation of this metal since its dyshomeostasis may favor the development of multiple diseases, such as Menkes’ and Wilson’s diseases, neurodegenerative diseases, diabetes mellitus, and cancer. As the relationship between Cu and cancer has been the most studied, we analyze how this metal can affect three fundamental processes for tumor progression: cell proliferation, angiogenesis, and metastasis. Gynecological diseases are characterized by high prevalence, morbidity, and mortality, depending on the case, and mainly include benign and malignant tumors. The cellular processes that promote their progression are affected by Cu, and the mechanisms that occur may be similar. We analyze the crosstalk between Cu deregulation and gynecological diseases, focusing on therapeutic strategies derived from this metal.

show abstract

Targeting copper metabolism: a promising strategy for cancer treatment

Cited by 16 publications

References 68 publications

Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Cuproptosis: Unraveling the Mechanisms of Copper-Induced Cell Death and Its Implication in Cancer Therapy

Copper in Gynecological Diseases

Copper in Gynecological Diseases

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