1. Copper and Colorectal Cancer.
- Author
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Małyszko, Maciej and Przybyłkowski, Adam
- Subjects
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COPPER metabolism , *RISK assessment , *COPPER , *CELL proliferation , *COLORECTAL cancer , *NEUROLOGICAL disorders , *METASTASIS , *CELL lines , *GENE expression , *CELL death , *PATHOLOGIC neovascularization , *DISEASE risk factors - Abstract
Simple Summary: Copper is a vital trace mineral supporting many body functions by acting as a cofactor for essential enzymes in energy production and antioxidant defense. It is mainly absorbed in the small intestine, and both its deficiency and excess can lead to serious health issues like neurological disorders and organ damage. In colorectal cancer (CRC), disruptions in copper metabolism play a significant role in tumor development and spread. A high copper concentration may facilitate cancer cell proliferation, angiogenesis, and metastasis. A newly discovered form of cell death called "cuproptosis" refers to a mitochondrial pathway of cell death triggered by excessive copper exposure and subsequent proteotoxic stress. Cuproplasia describes copper-dependent cell growth and proliferation, including hyperplasia, metaplasia, and neoplasia. Targeting copper concentration in the body is emerging as a promising strategy for CRC treatment. Therapies that reduce copper concentration using chelators or increase copper-induced cell death using ionophores have shown potential to inhibit tumor growth and enhance the effectiveness of existing treatments. Minerals constitute only 5% of the typical human diet but are vital for health and functionality. Copper, a trace element, is absorbed by the human gut at 30–40% from diets typical of industrialized countries. The liver produces metallothioneins, which store copper. Copper is crucial for mitochondrial respiration, pigmentation, iron transport, antioxidant defense, hormone production, and extracellular matrix biosynthesis. Copper deficiency, often caused by mutations in the ATP7A gene, results in Menkes disease, an X-linked recessive disorder. On the contrary, Wilson disease is characterized by toxic copper accumulation. Cuproptosis, a unique form of cell death regulated by copper, is a subtype of necrosis induced by enhanced mitochondrial metabolism and intracellular copper accumulation. This process can reduce the malignant potential of tumor cells by inhibiting glucose metabolism. Therapeutically, copper and its complexes have shown efficacy in malignancy treatments. The disruption of copper homeostasis and excessive cuproplasia are significant in colorectal cancer development and metastasis. Therefore, manipulating copper status presents a potential therapeutic target for colorectal cancer, using copper chelators to inhibit copper formation or copper ion carriers to promote cuproptosis. This review highlights the role of copper in human physiology and pathology, emphasizing its impact on colorectal cancer and potential therapeutic strategies. Future AI-based approaches are anticipated to accelerate the development of new compounds targeting cuproptosis and copper disruption in colorectal cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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