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As an essential nutrient, copper’s redox properties are both beneficial and toxic to cells. Therefore, leveraging the characteristics of copper-dependent diseases or using copper toxicity to treat copper-sensitive diseases may offer new strategies for specific disease treatments. In particular, copper concentration is typically higher in cancer cel...
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... carriers can increase the intracellular level of copper ions and exert anti-tumor effects by producing reactive oxygen species, inhibiting proteasomes, and inducing apoptosis (129,166). The schematic diagram is shown in Figure 3. Table 1 summarizes some FDAapproved and experimental drugs that target copper metabolism for the treatment of cancer. ...Citations
... Higher blood lead concentrations have been reported in PC cases, suggesting that environmental lead exposure may in uence prostate pathology risk. The consistent association of urinary lead with PC, even after adjustment for confounders, highlights its potential as a robust biomarker for prostate cancer risk [47,48]. ...
Heavy metals influence the development of several health conditions, including inflammation and cancer. This study investigates the relationship between heavy metal concentrations in plasma and urine, and the presence of benign prostatic hyperplasia (BPH), precancerous lesions (PL), and prostate cancer (PC). The influence of age, total PSA levels, hemoglobin concentrations, and the monocyte-to-lymphocyte ratio (MLR) is also analyzed across the three groups: BPH, PL, and PC. Our findings reveal significant differences in vanadium and antimony concentrations in plasma, suggesting a potential role in prostate disease pathophysiology. Notably, lower plasma antimony concentrations are associated with an increased risk of PC, while plasma vanadium concentrations are significantly higher in the PL group. Regression analysis further supports the association between heavy metal concentrations and the risk of PL and PC, highlighting the potential of vanadium and copper as biomarkers or therapeutic targets for prostate health. The study also explores the impact of lead exposure on prostate cancer risk, revealing a significant association between urine lead concentration and PC. These findings underscore the complex interaction between heavy metal concentrations and prostate disease risk, emphasizing the need for further research to elucidate underlying mechanisms and explore therapeutic interventions.
... Augmented copper levels can endocytose CTR1 from the plasma membrane, thereby preventing copper overload. After cellular uptake, Cu + can maintain extremely low intracellular free copper concentrations by binding to MT1/2 and GSH, protecting Cu + from disproportionation and then transferring Cu + to different copper chaperones (Tang et al., 2023). Free copper is extraordinarily reactive. ...
Colorectal cancer has emerged as one of the predominant malignant tumors globally. Immunotherapy, as a novel therapeutic methodology, has opened up new possibilities for colorectal cancer patients. However, its actual clinical efficacy requires further enhancement. Copper, as an exceptionally crucial trace element, can influence various signaling pathways, gene expression, and biological metabolic processes in cells, thus playing a critical role in the pathogenesis of colorectal cancer. Recent studies have revealed that cuproptosis, a novel mode of cell death, holds promise to become a potential target to overcome resistance to colorectal cancer immunotherapy. This shows substantial potential in the combination treatment of colorectal cancer. Conveying copper into tumor cells via a nano-drug delivery system to induce cuproptosis of colorectal cancer cells could offer a potential strategy for eliminating drug-resistant colorectal cancer cells and vastly improving the efficacy of immunotherapy while ultimately destroy colorectal tumors. Moreover, combining the cuproptosis induction strategy with other anti-tumor approaches such as photothermal therapy, photodynamic therapy, and chemodynamic therapy could further enhance its therapeutic effect. This review aims to illuminate the practical significance of cuproptosis and cuproptosis-inducing nano-drugs in colorectal cancer immunotherapy, and scrutinize the current challenges and limitations of this methodology, thereby providing innovative thoughts and references for the advancement of cuproptosis-based colorectal cancer immunotherapy strategies.
... Compared to normal cells, cancer cells are particularly reliant on copper, given their rapid proliferation and requirements for antioxidant defense due to their high metabolic demands. Liver, colorectal, lung, pancreas, and breast cancer tissues also have higher copper concentrations than normal tissues [11,12]. Such elevated copper levels have been found to be associated with the induction of malignant transformation in hepatocellular carcinoma and pancreatic ductal adenocarcinoma, indicating a strong link between copper homeostasis dysregulation and cancer occurrence [13,14]. ...
Copper is crucial for many physiological processes across mammalian cells, including energy metabolism, neurotransmitter synthesis, and antioxidant defense mechanisms. However, excessive copper levels can lead to cellular toxicity and “cuproptosis”, a form of programmed cell death characterized by the accumulation of copper within mitochondria. Tumor cells are less sensitive to this toxicity than normal cells, the mechanism for which remains unclear. We address this important issue by exploring the role of heat shock factor 1 (HSF1), a transcription factor that is highly expressed across several types of cancer and has a crucial role in tumor survival, in protecting against copper-mediated cytotoxicity. Using pancreatic ductal adenocarcinoma cells, we show that excessive copper triggers a proteotoxic stress response (PSR), activating HSF1 and that overexpressing HSF1 diminishes intracellular copper accumulation and prevents excessive copper-induced cell death and amyloid fibrils formation, highlighting HSF1′s role in preserving proteasomal integrity. Copper treatment decreases the lipoylation of dihydrolipoamide S-acetyltransferase (DLAT), an enzyme necessary for cuproptosis, induces DLAT oligomerization, and induces insoluble DLAT formation, which is suppressed by overexpressing HSF1, in addition to enhancing the interaction between HSF1 and DLAT. Our findings uncover how HSF1 protects against copper-induced damage in cancer cells and thus represents a novel therapeutic target for enhancing copper-mediated cancer cell death.
... Chelating copper has the potential to prolong the lifespan of individuals with advanced and challenging-to-treat malignancies, such as triple-negative breast cancer. 35 Liver diseases such as cirrhosis, obstructive jaundice, and cholestasis are associated with increased levels of Cu in the bloodstream. In newborns with jaundice, the elevated levels of Cu in the blood may originate from within the cells (specifically, red blood cells). ...
Objectives
Pre-hepatic jaundice results from an imbalance between bilirubin production and clearance, often linked to hemoglobinopathies. Antioxidant vitamin C, malondialdehyde, and trace elements play roles in jaundice, yet their specific associations remain unclear. The objective is to assess and compare these biomarkers in pre-hepatic jaundice patients and healthy controls, aiming to identify potential diagnostic markers and understand distinctive characteristics related to the disease’s pathogenesis.
Methods
This case–control study enrolled 50 pre-hepatic jaundice patients and 50 healthy controls, utilizing advanced techniques for biomarker quantification. We completed blood sample collection from study participants between 1 September 2023 and 31 December 2023. This study investigates the correlation between various biomarkers and pre-hepatic jaundice using serum samples with a focus on antioxidant vitamin C, malondialdehyde, and trace elements.
Results
This study demonstrates elevated concentrations of malondialdehyde in patients with pre-hepatic jaundice, suggesting alterations in bilirubin metabolism and increased oxidative stress. We found that the serum levels of malondialdehyde were significantly higher in pre-hepatic jaundice patients compared to healthy controls. Our observations revealed a notable decrease in the average serum vitamin C levels in patients with pre-hepatic jaundice compared to healthy controls. The patients had lower serum Zn levels and higher serum Cu and Mn levels compared to the healthy controls. The correlation study demonstrates robust positive correlations among these biomarkers in pre-hepatic jaundice. As the levels of vitamin C rise, the levels of the other criteria often fall, and vice versa. There is an inverse relationship between higher levels of vitamin C and lower levels of malondialdehyde. The current investigation identifies possible changes in antioxidant vitamins, malondialdehyde levels, and trace elements, which provide significant insights for targeted interventions.
Conclusions
The present research highlights the integrated significance of vitamin C, malondialdehyde, and trace elements in the progression of the disease.
... Copper is essential for various biological processes, including angiogenesis and oxidative stress response [21]. However, its role in cancer progression remains ambiguous. ...
Background: Lung cancer continues to be one of the most common causes of death due to lung malignancies globally. Emerging research suggests that vitamins and trace minerals, particularly antioxidants, may play a role in cancer progression and treatment outcomes. This study conducts a comparative analysis of vitamin D, folic acid, and trace minerals (copper, zinc, and magnesium) in various stages of lung cancer patients.
Methods: A cross-sectional study was conducted with 160 lung cancer patients, categorized into four stages (Stage 1 to Stage 4). Standardized biochemical assays, such as chemiluminescent immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and atomic absorption spectroscopy (AAS), were used to measure the levels of vitamin D, folic acid, copper (Cu), zinc (Zn), and magnesium (Mg) in the blood. The nutrient levels were compared across stages to investigate any significant variations.
Results: Vitamin D levels decreased significantly as lung cancer progressed, with Stage 1 showing the highest mean level (33 ng/mL) and Stage 4 the lowest (8 ng/mL). Folic acid levels fluctuated, showing a general decrease in the advanced stages, with some variations in the intermediate stages. Copper levels showed individual variability without a consistent trend across stages. Zinc levels were higher in early-stage patients and decreased as cancer progressed. Magnesium levels remained relatively stable across all stages.
Conclusion: This comparative analysis highlights the potential significance of monitoring vitamin D, folic acid, and trace minerals in lung cancer patients across different stages. The results suggest that these nutrients may play a role in the progression of lung cancer and could serve as biomarkers for disease staging.
... These results suggest that the compounds could be used as growth activators or inhibitors, depending on the concentration, thereby offering potential applications in agriculture and biotechnology ( Fig. 1 -2). which is potentially usable for modulating cell growth [27,28]. Different forms of Cu can have both growth activator and inhibitory influence on fungi [29,30]. ...
Background: Pursuing alternative starting materials has gained significant importance in the food and drug industries, driven by the global shift towards sustainable and renewable resources. Terpenes, naturally occurring hydrocarbons derived from plants, present a promising solution due to their abundant availability and range of physiological activities, including antioxidant, anti-inflammatory, antimicrobial, and anticancer properties. Objective: This study aims to develop a waste-free synthesis methodology for functionalizing limonene and myrcene, two notable terpenes, through Atom Transfer Radical Reactions (ATRR). The objective is to achieve high yields and purities while enhancing the therapeutic potential of these compounds and adhering to green chemistry principles. Methods: A catalytic complex of Cu(I)Br and dimethyl sulfoxide (DMSO) was used to facilitate the coupling of limonene and myrcene with various trichloroacetic acid derivatives. Reactions were performed at 80°C for 90 minutes, and products were purified by column chromatography. The synthesized compounds were characterized using Gas Chromatography-Mass Spectrometry (GC-MS) and Nuclear Magnetic Resonance (NMR). Microbiological analyses were conducted using the disk-diffusion method, and statistical analyses were performed to assess the reliability of the experiments. Results: The ATRR methodology enabled the efficient functionalization of limonene and myrcene, achieving high yields and purities. The best yield for limonene was 70%, and for myrcene, 82%, both using trichloroacetonitrile. The Cu(I) catalytic system showed dualistic biological effects, with 3% concentration exhibiting strong bactericidal and fungicidal activity, while 0.03% promoted growth. These results demonstrate the potential of the methodology and the catalytic system for bioactive compound synthesis and agricultural applications. Conclusion: This study demonstrates the viability of ATRR for efficiently functionalizing limonene and myrcene, achieving high yields and purities. The synthesized compounds show promise for pharmaceutical development. The dual antibacterial and antifungal activities of the Cu(I) catalytic system also suggest potential applications in wastewater reutilization. Future work should explore the biological effects and environmental impact of this process. Keywords: Terpenes, ATR reactions, Green Chemistry, Bioactive compounds, Therapeutic potential.
... A deficiency in magnesium could impair these critical processes, leading to cellular dysfunction, which may contribute to the progression of cancer by compromising the body's ability to regulate cell growth and repair damaged DNA [23][24]. This finding supports the potential benefit of Mg supplementation, especially for patients in advanced stages of IDC [25][26]. ...
Background: Invasive ductal carcinoma (IDC) is one of the most commonly diagnosed subtypes of breast cancer, representing the majority of breast cancer cases. This study investigates the levels of vitamin D, folic acid, and antioxidant minerals (zinc (Zn), copper (Cu), and magnesium (Mg)) in IDC patients across different disease stages to explore their potential roles in disease progression.
Methods: We analyzed a cohort of 150 female patients with IDC, aged between 30 and 67 years (51 ± 15.5 years). Blood samples were collected to measure levels of vitamin D, folic acid, Cu, Mg, and Zn. Patients were categorized into Stage 1 to Stage 4 of cancer. Variations in nutrient levels across these stages were statistically assessed using ANOVA and post-hoc tests.
Results: The study results revealed varying levels of key nutrients across different stages of the disease. Vitamin D levels averaged 17.7 ng/mL, with higher concentrations in early-stage patients, indicating a possible correlation with disease severity. Folic acid levels had a mean of 12.2 ng/mL, showing a decline in later stages, potentially linking it to cancer progression. Copper levels averaged 161.3μg/dL, peaking at 170μg/dL in Stage 3, suggesting a connection with cancer aggressiveness. Magnesium levels, with an average of 1.4 mg/dL, dropped notably to 0.6 mg/dL by Stage 4, highlighting its possible involvement in disease progression. Zinc levels averaged 69.4 μg/dL, with a significant decrease in advanced stages, emphasizing its importance for immune function and cellular health.
Conclusion: The study demonstrates significant variations in the levels of vitamin D, folic acid, and antioxidant minerals across different stages of IDC. These nutrients may influence cancer progression, underscoring the potential benefits of nutritional assessments and interventions in managing IDC.
... These findings demonstrated the significant potential of copper in treating malignancies that have an inherent resistance to apoptosis. Recent research has identified the ubiquitin-proteasome system (UPS), copper deficiencyinduced angiogenesis suppression in cancer cells, and cuproptosis as the main mechanisms of copper-inducing cancer cell death [49]. ...
Copper is a vital trace element in oxidized and reduced forms. It plays crucial roles in numerous biological events such as redox chemistry, enzymatic reactions, mitochondrial respiration, iron metabolism, autophagy, and immune modulation. Maintaining the balance of copper in the body is essential because its deficiency and excess can be harmful. Abnormal copper metabolism has a two-fold impact on the development of tumors and cancer treatment. Cuproptosis is a form of cell death that occurs when there is excessive copper in the body, leading to proteotoxic stress and the activation of a specific pathway in the mitochondria. Research has been conducted on the advantageous role of copper ionophores and chelators in cancer management. This review presents recent progress in understanding copper metabolism, cuproptosis, and the molecular mechanisms involved in using copper for targeted therapy in cervical cancer. Integrating trace metals and minerals into nanoparticulate systems is a promising approach for controlling invasive tumors. Therefore, we have also included a concise overview of copper nanoformulations targeting cervical cancer cells. This review offers comprehensive insights into the correlation between cuproptosis-related genes and immune infiltration, as well as the prognosis of cervical cancer. These findings can be valuable for developing advanced clinical tools to enhance the detection and treatment of cervical cancer.
... However, the nutritional significance of perilla encompasses not only its fatty acid and protein content but also includes a diverse array of essential minerals crucial for human health, including calcium, copper, magnesium, manganese, phosphorus, and zinc. These minerals are important for various physiological and metabolic processes in both humans and animals González-Montaña et al., 2020;Long and Romani, 2014;Tang et al., 2023). Despite its mineral-rich potential, utilization of perilla remains underexplored, primarily due to the predominant focus on its oil content, leading to the discarding of the defatted seed meal (Kim et al., 2019;Kim and Yoon, 2020). ...
... Copper acts as a cofactor in enzymes such as cytochrome c oxidase, vital for cellular respiration, and superoxide dismutase, essential for antioxidant defense against free radicals. It also facilitates reactions in enzymes like tyrosinase, involved in melanin production, and lysyl oxidase, vital for connective tissue formation Tang et al., 2023). Copper content exhibited variability as well, with concentrations ranging from 11 ppm to 19 ppm, and a mean of 15 ppm. ...
Perilla seeds contain a rich array of essential minerals, thus having the potential to address multiple micronutrient deficiencies at a time. However, traditional methods of mineral estimation are complex, time-consuming, expensive, and require technical expertise. This study includes the development of Near-Infrared Reflectance Spectroscopy (NIRS)-based prediction models for predicting five important minerals (Calcium, Copper, Magnesium, Manganese, and Phosphorus) using machine learning and deep learning techniques. Four models, including 1D Convolutional Neural Networks (1D CNNs), Artificial Neural Networks (ANNs), Random Forests (RFs), and Support Vector Regression (SVR), were developed and evaluated. The developed 1D CNN model outperformed other considered models in predicting calcium, magnesium, and phosphorus content with RPD (Residual Prediction Deviation) values of 1.75, 1.83, and 2.96, respectively. Whereas SVR performed best in predicting copper and manganese with an RPD of 1.82 and 2.2, respectively. The 1D CNN model demonstrated R2 (Coefficient of determination) values above 0.65 for all minerals, with a maximum of 0.88 for phosphorus. In addition, the developed models performed superior as compared to the Partial Least Square Regression method (R2= 0.32). The developed models provide efficient tools for rapidly screening perilla germplasm available in global repositories, thus aiding in the selection of mineral-rich genotypes to mitigate micronutrient deficiencies.
... Hypoxia-inducible factor 1-alpha (HIF-1α) can indirectly stabilize and activate the transcription of many genes involved in copper metabolism, including those controlling CTR1, thereby contributing to higher copper levels in cancer cells. Indeed, CTR1 expression is increased in various cancers [63]. ...
Selenium (Se), zinc (Zn), and copper (Cu) are known to be involved in carcinogenesis and participate in the defence against reactive oxygen species (ROS). This study aimed to evaluate the clinical utility of serum Se, Zn, and Cu concentrations and plasma total antioxidant status (TAS) in the diagnosis of colorectal cancer (CRC) and colorectal adenoma (CRA) in a population of low Se and borderline Zn status. Based on clinical examination and colonoscopy/histopathology, the patients (n = 79) were divided into three groups: colorectal cancer (n = 30), colorectal adenoma (n = 19), and controls (CONTROL, n = 30). The serum Se concentration was lower in the CRC group than in the CRA group (by 9.1%, p < 0.0001) and the CONTROL group (by 7.9%, p < 0.0001). In turn, the serum Zn concentration was decreased in the CRA group (by 17.9%, p = 0.019) when compared to the CONTROL group. Plasma TAS was lower in the CRC group (by 27.8%, p = 0.017) than in the CONTROL group. In turn, the serum Zn concentration was decreased in the CRA group when compared to the CONTROL group. Plasma TAS was lower in the CRC group than in the CONTROL group. ROC (receiver operating characteristic) curve analysis revealed that the Se level was of the highest diagnostic utility for the discrimination of the CRC group from both the CRA group (area under ROC curve (AUC) 0.958, sensitivity 84.21%, specificity 100%) and the CONTROL group (AUC 0.873, sensitivity 100%, specificity 66.67%). The Zn and TAS levels were significantly accurate in the differentiation between the groups. An individualised risk of colorectal adenoma and cancer approach could comprise Se, Zn, and TAS assays in the population.