Copper homeostasis: Emerging target for cancer treatment

Li, Yueqin

doi:10.1002/iub.2341

Cited by 157 publications

(125 citation statements)

References 86 publications

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“…Copper is a potent stimulator of the angiogenic process by the activation of angiogenic factors like the interleukin (IL)-1, IL-6, and IL-8; tumor necrosis factor alpha (TNF-α); angiogenin; the basic fibroblast growth factor (bFGF); fibronectin; and the vascular endothelial growth factor (VEGF), which are critical for tumor angiogenic developments ( Li 2020 ). Copper sulfate (CuSO 4 ) combined with increasing doses of VEGF or FGF-2 revealed synergistic effect in endothelial cells grown in a 3D culture system with enhanced collagen fiber deposition providing complexity of angiogenic networks ( Gérard et al, 2010 ).…”

Section: Copper Role In Cancermentioning

confidence: 99%

Role of Copper on Mitochondrial Function and Metabolism

Ruíz

Libedinsky

Elorza

2021

Front. Mol. Biosci.

215

174

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Copper is essential for life processes like energy metabolism, reactive oxygen species detoxification, iron uptake, and signaling in eukaryotic organisms. Mitochondria gather copper for the assembly of cuproenzymes such as the respiratory complex IV, cytochrome c oxidase, and the antioxidant enzyme superoxide dismutase 1. In this regard, copper plays a role in mitochondrial function and signaling involving bioenergetics, dynamics, and mitophagy, which affect cell fate by means of metabolic reprogramming. In mammals, copper homeostasis is tightly regulated by the liver. However, cellular copper levels are tissue specific. Copper imbalances, either overload or deficiency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity. Consistently, new pharmacological developments have been addressed to reduce or exacerbate copper levels as potential cancer therapies. This review goes over the copper source, distribution, cellular uptake, and its role in mitochondrial function, metabolic reprograming, and cancer biology, linking copper metabolism with the field of regenerative medicine and cancer.

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Section: Copper Role In Cancermentioning

confidence: 99%

Role of Copper on Mitochondrial Function and Metabolism

Ruíz

Libedinsky

Elorza

2021

Front. Mol. Biosci.

215

174

View full text Add to dashboard Cite

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“…Furthermore, it should be considered that most of the metal‐binding compounds possess a Brønsted base character, making them highly sensitive to pH variation, with great implications for the treatment of several pathological conditions [53] . Due to the integration of copper ions into multiple cellular pathways, both copper chelators and ionophores showed promising effects in cancer treatment [54] . In particular, the benefits of reducing copper bioavailability in cancer has been demonstrated using D‐PEN (D‐penicillamine), TETA (triethylenetetramine) or TM (tetrathiomolybdate) with key reductions in tumor vessel diameter, endothelial cell proliferation and activation of CD4 + T‐cells alongside their increased infiltration observed [55] (Figure 2).…”

Section: Coppermentioning

confidence: 99%

Copper: An Intracellular Achilles’ Heel Allowing the Targeting of Epigenetics, Kinase Pathways, and Cell Metabolism in Cancer Therapeutics

et al. 2021

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Copper is an essential transition metal frequently increased in cancer known to strongly influence essential cellular processes. Targeted therapy protocols utilizing both novel and repurposed drug agents initially demonstrate strong efficacy, before failing in advanced cancers as drug resistance develops and relapse occurs. Overcoming this limitation involves the development of strategies and protocols aimed at a wider targeting of the underlying molecular changes. Receptor Tyrosine Kinase signaling pathways, epigenetic mechanisms and cell metabolism are among the most common therapeutic targets, with molecular investigations increasingly demonstrating the strong influence each mechanism exerts on the others. Interestingly, all these mechanisms can be influenced by intracellular copper. We propose that copper chelating agents, already in clinical trial for multiple cancers, may simultaneously target these mechanisms across a wide variety of cancers, serving as an excellent candidate for targeted combination therapy. This review summarizes the known links between these mechanisms, copper, and copper chelation therapy.

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“…Multiple types of tumors (e.g., breast and colorectal cancers) have aberrantly elevated copper levels, which promote tumor progression by increasing cell proliferation and stimulating angiogenesis and metastasis (Denoyer et al, 2015;Li, 2020;Shanbhag et al, 2020). This abnormal copper pathway in cancer can be targeted by two strategies.…”

Section: Copper Complexes As Ups Inhibitors In Cancer Treatmentmentioning

confidence: 99%

Targeting Ubiquitin–Proteasome System With Copper Complexes for Cancer Therapy

Chen

Dou

Liu

et al. 2021

Front. Mol. Biosci.

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Characterizing mechanisms of protein homeostasis, a process of balancing between protein synthesis and protein degradation, is important for understanding the potential causes of human diseases. The ubiquitin–proteasome system (UPS) is a well-studied mechanism of protein catabolism, which is responsible for eliminating misfolded, damaged, or aging proteins, thereby maintaining quality and quantity of cellular proteins. The UPS is composed of multiple components, including a series of enzymes (E1, E2, E3, and deubiquitinase [DUB]) and 26S proteasome (19S regulatory particles + 20S core particle). An impaired UPS pathway is involved in multiple diseases, including cancer. Several proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, are approved to treat patients with certain cancers. However, their applications are limited by side effects, drug resistance, and drug–drug interactions observed in their clinical processes. To overcome these shortcomings, alternative UPS inhibitors have been searched for in many fields. Copper complexes (e.g., CuET, CuHQ, CuCQ, CuPDTC, CuPT, and CuHK) are found to be able to inhibit a core component of the UPS machinery, such as 20S proteasome, 19S DUBs, and NPLOC4/NPL4 complex, and are proposed to be one class of metal-based anticancer drugs. In this review, we will summarize functions and applications of copper complexes in a concise perspective, with a focus on connections between the UPS and cancer.

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Copper homeostasis: Emerging target for cancer treatment

Cited by 157 publications

References 86 publications

Role of Copper on Mitochondrial Function and Metabolism

Role of Copper on Mitochondrial Function and Metabolism

Copper: An Intracellular Achilles’ Heel Allowing the Targeting of Epigenetics, Kinase Pathways, and Cell Metabolism in Cancer Therapeutics

Targeting Ubiquitin–Proteasome System With Copper Complexes for Cancer Therapy

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