Induction of oxidative damage by copper-based antineoplastic drugs (Casiopeínas®)

Alemón-Medina, Radamés; Breña-Valle, Matilde; Muñoz-Sánchez, José Luis; Gracia-Mora, María Isabel; Ruíz-Azuara, Lena

doi:10.1007/s00280-006-0364-9

Cited by 100 publications

(50 citation statements)

References 29 publications

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“…[Cu(CH 3 COO) 2 (phen)] (9a) displayed potent in vitro cytotoxicity against human hepatic Hep-G, renal A-498, and lung A-549 cancer cell lines, approximately seven times higher than that shown by cisplatin. 215 A series of copper-based drugs registered with the name of Casiopeinas s (Cas) has been developed by Ruiz-Azuara et al 216 These compounds are mixed-chelate copper(II) complexes with a general condensed formula [Cu (N-N) 216 Experiments in rats employing one of the most promising derivatives (9b), showed a strong antitumor activity against C6 glioma cells 217 evidenced by significant decrease in tumor volume, mitotic, and proliferation indexes. These effects were accompanied by a limited general toxicity in tumor bearing rats.…”

Section: (Mal)]mentioning

confidence: 99%

Copper in diseases and treatments, and copper‐based anticancer strategies

Tisato¹,

Marzano

Porchia³

et al. 2009

Medicinal Research Reviews

628

444

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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.

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Section: (Mal)]mentioning

confidence: 99%

Copper in diseases and treatments, and copper‐based anticancer strategies

Tisato¹,

Marzano

Porchia³

et al. 2009

Medicinal Research Reviews

628

444

View full text Add to dashboard Cite

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“…Outstanding examples of active Cu-complexes are the coordination compounds known as Casiopeinas®, developed by L. Ruiz and co-workers, two of which are already approved for clinical trials as antitumor drugs, [(Cu(II))(4,7-dimethyl-phen)(glycinate)(NO 3 )(H 2 O)] and [(Cu(II))(4,4′-dimethyl-2,2′-bipyridine)(acetylacetonate)(NO 3 )(H 2 O)] [4]. The proposed mechanism of action of these complexes involves oxidative damage, due to intracellular formation of reactive oxygen species (ROS) and DNA interaction, leading to apoptosis of the cells [5]. In addition to Cu(II) complexes, Cu(I) complexes also show antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, structural characterization and cytotoxic activity of ternary copper(II)–dipeptide–phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer

Iglesias¹,

Álvarez²,

Torre³

et al. 2014

Journal of Inorganic Biochemistry

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“…These copper complexes have been developed primarily for their action against cancerous tumors [14,15,16] in in vitro and in vivo models. Although the action mechanism is not known in detail, at the molecular level, several results support that these compounds are able to inhibit cell proliferation mainly by apoptotic pathways [15,16], that participate in redox reactions that produce reactive oxygen species [15,16] and interact directly with DNA and its constituents [17].…”

Section: Introductionmentioning

confidence: 99%

Potential of Casiopeínas® Copper Complexes and Antituberculosis Drug Combination against <b><i>Mycobacterium tuberculosis</i></b>

Barbosa¹,

Caleffi-Ferracioli

Leite

et al. 2016

Chemotherapy

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New compounds with antituberculosis activity and their combination with classic drugs have been evaluated to determine possible interactions and antagonism. The aim of this study was to evaluate the in vitro activity of Casiopeínas® copper-based compounds (CasIIIia, CasIIIEa, and CasIIgly) alone and combined with isoniazid (INH), rifampicin, or ethambutol (EMB) against resistant and susceptible Mycobacterium tuberculosis. Seventeen clinical M. tuberculosis isolates (5 multi-drug resistant and 2 resistant to INH and/or EMB) were subjected to determination of the minimal inhibitory concentration (MIC) by the resazurin microtiter assay and combination assessment by the resazurin drug combination microtiter assay. The Casiopeínas® alone showed a remarkable effect against resistant isolates with MIC values from 0.78 to 12.50 μg/ml. Furthermore, a synergistic effect mainly with EMB is shown for both resistant and susceptible clinical isolates. Casiopeínas® are promising candidates for future investigation into the development of antituberculosis drugs, being one of the first examples of essential metal-based drugs used in this field.

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Induction of oxidative damage by copper-based antineoplastic drugs (Casiopeínas®)

Abstract: These results suggest that ROS generation might be the cause of cytotoxicity, which seems to be related to initial genetic damage rather than to lipid peroxidation. HeLa cells showed to be more sensitive than normal cells.

Cited by 100 publications

References 29 publications

Copper in diseases and treatments, and copper‐based anticancer strategies

Copper in diseases and treatments, and copper‐based anticancer strategies

Synthesis, structural characterization and cytotoxic activity of ternary copper(II)–dipeptide–phenanthroline complexes. A step towards the development of new copper compounds for the treatment of cancer

Potential of Casiopeínas® Copper Complexes and Antituberculosis Drug Combination against <b><i>Mycobacterium tuberculosis</i></b>

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