Copper levels in patients with hematological malignancies

Kaiafa, Georgia; Saouli, Zoi; Diamantidis, Michael D.; Kontoninas, Zisis; Voulgaridou, Virginia; Raptaki, Maria; Arampatzi, Stergiani; Chatzidimitriou, Maria; Perifanis, Vassilios

doi:10.1016/j.ejim.2012.07.009

Cited by 51 publications

(43 citation statements)

References 20 publications

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“…7 Moreover, copper levels have been observed to decrease in instances of remission in patients with hematological malignacies, such as, chronic lymphoid leukemia, non-Hodgkin's lymphoma, multiplemyeloma and Hodgkin's lymphoma. 68 Interestingly, the relapse of disease correlated with an increase in copper levels. 68 The significance of copper in cancer is further exemplified in a study by Majumder et al, where patients presenting with advanced cancers of the breast, lung, and colon that experienced drug resistance, had approximately 130-160% more copper in their serum.…”

Section: Copper and Its Link To Cancermentioning

confidence: 98%

“…68 Interestingly, the relapse of disease correlated with an increase in copper levels. 68 The significance of copper in cancer is further exemplified in a study by Majumder et al, where patients presenting with advanced cancers of the breast, lung, and colon that experienced drug resistance, had approximately 130-160% more copper in their serum. 69 Moreover, high copper levels are considered carcinogenic, and are suspected to encourage tumour progression through the production of reactive oxygen species (ROS; for an in-depth review see 70 ).…”

Section: Copper and Its Link To Cancermentioning

confidence: 98%

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Copper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics

et al. 2016

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Copper is an essential trace metal required by organisms to perform a number of important biological processes. Copper readily cycles between its reduced Cu(i) and oxidised Cu(ii) states, which makes it redox active in biological systems. This redox-cycling propensity is vital for copper to act as a catalytic co-factor in enzymes. While copper is essential for normal physiology, enhanced copper levels in tumours leads to cancer progression. In particular, the stimulatory effect of copper on angiogenesis has been established in the last several decades. Additionally, it has been demonstrated that copper affects tumour growth and promotes metastasis. Based on the effects of copper on cancer progression, chelators that bind copper have been developed as anti-cancer agents. In fact, a novel class of thiosemicarbazone compounds, namely the di-2-pyridylketone thiosemicarbazones that bind copper, have shown great promise in terms of their anti-cancer activity. These agents have a unique mechanism of action, in which they form redox-active complexes with copper in the lysosomes of cancer cells. Furthermore, these agents are able to overcome P-glycoprotein (P-gp) mediated multi-drug resistance (MDR) and act as potent anti-oncogenic agents through their ability to up-regulate the metastasis suppressor protein, N-myc downstream regulated gene-1 (NDRG1). This review provides an overview of the metabolism and regulation of copper in normal physiology, followed by a discussion of the dysregulation of copper homeostasis in cancer and the effects of copper on cancer progression. Finally, recent advances in our understanding of the mechanisms of action of anti-cancer agents targeting copper are discussed.

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Section: Copper and Its Link To Cancermentioning

confidence: 98%

Section: Copper and Its Link To Cancermentioning

confidence: 98%

Copper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics

et al. 2016

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“…Abnormal angiogenesis has been implicated in many diseases including cancer, heart diseases, stroke, diabetes, and blindness. Various types of tumors, such as carcinoma of breast, bladder, chronic lymphoid leukemia, prostate, colon, lung, and brain tumors show high Cu levels in serum and tissues . In addition, it is reported that Cu levels increase with the disease progression .…”

Section: Introductionmentioning

confidence: 99%

Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Narayanan

Natarajan

2017

Chem Biol Drug Des

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Angiogenesis is a process of synthesis of new blood vessels from preexisting vasculature. Copper (Cu) as a micronutrient is important to many proteins for their physiological roles. Cu is transported by ceruloplasmin from liver to other parts of the body. Copper transporter 1 (CTR1) is a transmembrane protein which participate in Cu transport across the cell. It is also known to be involved in angiogenesis. In this study, we have designed three peptides from copper-binding regions of CTR1 which are rich in histidine and methionine. These peptides were screened for their inhibitory effect on angiogenesis in the HUVEC model. Mass spectroscopy studies revealed that all the three peptides derived from CTR 1 (Pep 1, 2, and 3) bound to Cu. The intracellular Cu levels estimated by atomic absorption spectroscopy showed decreased levels of copper in peptide-treated cells as compared to control. These peptides inhibited proliferation, migration, and tube formation in HUVEC by sequestering copper, preventing its entry into the cell and thereby inhibiting angiogenesis.

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“…Increased copper content has been determined in serum [92] and tissue samples [93] from patients with different types of cancer, including laryngeal squamous cell carcinoma [94], non-Hodgkin's lymphoma [95], multiple myeloma [96], chronic lymphocytic leukemia [97], hepatocellular carcinoma [98], gynecological carcinoma [99], colorectal [100], lung [101], primary brain [102], and breast [103] cancers. Serum copper levels return to normal upon successful tumor surgical removal or on remission.…”

Section: Cancermentioning

confidence: 99%

Current Biomedical Use of Copper Chelation Therapy

Baldari

Rocco

Toietta

2020

IJMS

124

105

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Copper is an essential microelement that plays an important role in a wide variety of biological processes. Copper concentration has to be finely regulated, as any imbalance in its homeostasis can induce abnormalities. In particular, excess copper plays an important role in the etiopathogenesis of the genetic disease Wilson’s syndrome, in neurological and neurodegenerative pathologies such as Alzheimer’s and Parkinson’s diseases, in idiopathic pulmonary fibrosis, in diabetes, and in several forms of cancer. Copper chelating agents are among the most promising tools to keep copper concentration at physiological levels. In this review, we focus on the most relevant compounds experimentally and clinically evaluated for their ability to counteract copper homeostasis deregulation. In particular, we provide a general overview of the main disorders characterized by a pathological increase in copper levels, summarizing the principal copper chelating therapies adopted in clinical trials.

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Copper levels in patients with hematological malignancies

Cited by 51 publications

References 20 publications

Copper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics

Copper and conquer: copper complexes of di-2-pyridylketone thiosemicarbazones as novel anti-cancer therapeutics

Peptides derived from histidine and methionine‐rich regions of copper transporter 1 exhibit anti‐angiogenic property by chelating extracellular Cu

Current Biomedical Use of Copper Chelation Therapy

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