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Copper in diseases and treatments, and copper-based anticancer strategies.
Med Res Rev. 2010 Jul; 30(4):708-49.MR

Abstract

Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects.

Authors+Show Affiliations

ICIS-CNR, Corso Stati Uniti 4, Padova 35127, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

19626597

Citation

Tisato, Francesco, et al. "Copper in Diseases and Treatments, and Copper-based Anticancer Strategies." Medicinal Research Reviews, vol. 30, no. 4, 2010, pp. 708-49.
Tisato F, Marzano C, Porchia M, et al. Copper in diseases and treatments, and copper-based anticancer strategies. Med Res Rev. 2010;30(4):708-49.
Tisato, F., Marzano, C., Porchia, M., Pellei, M., & Santini, C. (2010). Copper in diseases and treatments, and copper-based anticancer strategies. Medicinal Research Reviews, 30(4), 708-49. https://doi.org/10.1002/med.20174
Tisato F, et al. Copper in Diseases and Treatments, and Copper-based Anticancer Strategies. Med Res Rev. 2010;30(4):708-49. PubMed PMID: 19626597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Copper in diseases and treatments, and copper-based anticancer strategies. AU - Tisato,Francesco, AU - Marzano,Cristina, AU - Porchia,Marina, AU - Pellei,Maura, AU - Santini,Carlo, PY - 2009/7/24/entrez PY - 2009/7/25/pubmed PY - 2010/9/24/medline SP - 708 EP - 49 JF - Medicinal research reviews JO - Med Res Rev VL - 30 IS - 4 N2 - Copper is found in all living organisms and is a crucial trace element in redox chemistry, growth and development. It is important for the function of several enzymes and proteins involved in energy metabolism, respiration, and DNA synthesis, notably cytochrome oxidase, superoxide dismutase, ascorbate oxidase, and tyrosinase. The major functions of copper-biological molecules involve oxidation-reduction reactions in which they react directly with molecular oxygen to produce free radicals. Therefore, copper requires tightly regulated homeostatic mechanisms to ensure adequate supplies without any toxic effects. Overload or deficiency of copper is associated, respectively, with Wilson disease (WD) and Menkes disease (MD), which are of genetic origin. Researches on Menkes and Wilson disorders have provided useful insights in the field of copper homeostasis and in particular into the understanding of intracellular trafficking and distribution of copper at molecular levels. Therapies based on metal supplementation with copper histidine or removal of copper excess by means of specific copper chelators are currently effective in treating MD and WD, respectively. Copper chelation therapy is now attracting much attention for the investigation and treatment of various neurodegenerative disorders such as Alzheimer, Parkinson and CreutzfeldtJakob. An excess of copper appears to be an essential co-factor for angiogenesis. Moreover, elevated levels of copper have been found in many types of human cancers, including prostate, breast, colon, lung, and brain. On these basis, the employment of copper chelators has been reported to be of therapeutic value in the treatment of several types of cancers as anti-angiogenic molecules. More recently, mixtures of copper chelators with copper salts have been found to act as efficient proteasome inhibitors and apoptosis inducers, specifically in cancer cells. Moreover, following the worldwide success of platinum(II) compounds in cancer chemotherapy, several families of individual copper complexes have been studied as potential antitumor agents. These investigations, revealing the occurrence of mechanisms of action quite different from platinum drugs, head toward the development of new anticancer metallodrugs with improved specificity and decreased toxic side effects. SN - 1098-1128 UR - https://www.unboundmedicine.com/medline/citation/19626597/Copper_in_diseases_and_treatments_and_copper_based_anticancer_strategies_ L2 - https://doi.org/10.1002/med.20174 DB - PRIME DP - Unbound Medicine ER -