Metal ionophores - an emerging class of anticancer drugs.
Compounds that bind metals such as copper and zinc have many biological activities, including the ability to induce apoptosis in cancer cells. Although some of these compounds have been considered to act as chelators of metals, decreasing their bioavailability, others increase intracellular metal concentrations. We review recent work regarding the recognition of the biological effects of metal ionophores with different structures, particularly with regard to their actions upon cancer cells focusing on dithiocarbamates, pyrithione, and the 8-hydroxyquinoline derivative, clioquinol. We provide a biologically based classification of metal-binding compounds that allows an experimental distinction between chelators and ionophores that can be readily used by biologists, which may lead to further study and classification of metal-binding drugs. Metal ionophores may kill cancer cells by a number of mechanisms, including lysosomal disruption and proteasome inhibition, and likely others. Because some of these compounds have been safely administered to animals and humans, they have the potential to become clinically useful anticancer agents.
Ding
Wei-Qun
WQ
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. weiqun-ding@ouhsc.edu
Lind
Stuart E
SE
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D007464:Clioquinol / Q000494:pharmacology; D006801:Humans; D007476:Ionophores / Q000378:metabolism / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D008670:Metals / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D061988:Proteasome Inhibitors; D011725:Pyridines; D013871:Thiones; D015032:Zinc / Q000378:metabolism
D000970:Antineoplastic Agents; D002614:Chelating Agents; D007476:Ionophores; D008670:Metals; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011725:Pyridines; D013871:Thiones; C008704:pyrithione; D007464:Clioquinol; D015032:Zinc