Abstract
The chemical properties of copper allow it to take part in many biological functions such as electron transfer, catalysis, and structural shaping. The ability to cycle between +1 and +2 oxidation state is one of the features that has been exploited by organisms throughout the evolutionary process. Since copper is potentially toxic to cells also a finely controlled mechanism for copper handling has evolved. On the other side, many copper complexes were synthesized and tested for their anticancer activity in vitro and in vivo. Their ability to kill cancer cells is mainly related to the induction of an oxidative stress, but recently it emerged their ability to inhibit the proteasome, a protein complex whose proteolitic activity is needed by several cellular process. It has generally been described that the toxic effects of copper complexes leads to cell death either by necrosis or through the activation of the apoptotic process. Evidences are rising about the ability of some copper compounds to induce alternative non-apoptotic form of programmed cell death. Since copper is indispensable for the formation of new blood vessels, angiogenesis, a different antitumor approach based on the administration of copper sequestering agents has been attempted and its effectiveness is currently under evaluation by clinical trials. The proven essentiality of copper for angiogenesis, together with the marked sensitivity shown by several cancer cell lines to the copper toxicity, open a new perspective in the anticancer strategy: exploiting the tumor need of copper to accumulate toxic amount of the metal inside its cells.
Keywords: Copper complex, ROS, proteasome inhibition, apoptosis, paraptosis
Current Medicinal Chemistry
Title: Copper Compounds in Anticancer Strategies
Volume: 16 Issue: 11
Author(s): Saverio Tardito and Luciano Marchio
Affiliation:
Keywords: Copper complex, ROS, proteasome inhibition, apoptosis, paraptosis
Abstract: The chemical properties of copper allow it to take part in many biological functions such as electron transfer, catalysis, and structural shaping. The ability to cycle between +1 and +2 oxidation state is one of the features that has been exploited by organisms throughout the evolutionary process. Since copper is potentially toxic to cells also a finely controlled mechanism for copper handling has evolved. On the other side, many copper complexes were synthesized and tested for their anticancer activity in vitro and in vivo. Their ability to kill cancer cells is mainly related to the induction of an oxidative stress, but recently it emerged their ability to inhibit the proteasome, a protein complex whose proteolitic activity is needed by several cellular process. It has generally been described that the toxic effects of copper complexes leads to cell death either by necrosis or through the activation of the apoptotic process. Evidences are rising about the ability of some copper compounds to induce alternative non-apoptotic form of programmed cell death. Since copper is indispensable for the formation of new blood vessels, angiogenesis, a different antitumor approach based on the administration of copper sequestering agents has been attempted and its effectiveness is currently under evaluation by clinical trials. The proven essentiality of copper for angiogenesis, together with the marked sensitivity shown by several cancer cell lines to the copper toxicity, open a new perspective in the anticancer strategy: exploiting the tumor need of copper to accumulate toxic amount of the metal inside its cells.
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Cite this article as:
Tardito Saverio and Marchio Luciano, Copper Compounds in Anticancer Strategies, Current Medicinal Chemistry 2009; 16 (11) . https://dx.doi.org/10.2174/092986709787846532
DOI https://dx.doi.org/10.2174/092986709787846532 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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