Zinc-binding compounds induce cancer cell death via distinct modes of action.
Metal-binding compounds have been shown to have anticancer activity and are being evaluated clinically as anticancer agents. We have recently found that a zinc-binding compound, 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol), kills cancer cells by transporting zinc into the cells. We therefore compared the action of clioquinol with two other cytotoxic zinc-binding compounds, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and pyrrolidine dithiocarbamate (PDTC). We demonstrate that metal-binding compounds can be subclassified based upon the reversibility of their cytotoxicity by metal supplementation and their modes of action. Understanding the mechanisms whereby metal-binding compounds affect cell behavior may aid in their optimization for clinical use.
Ding
Wei-Qun
WQ
Department of Pathology, University of Oklahoma Health Sciences Center, 975 NE 10th Street, BRC 411A, Oklahoma City, OK 73104, USA. weiqun-ding@ouhsc.edu
Yu
Hai-Jun
HJ
Lind
Stuart E
SE
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D007464:Clioquinol / Q000378:metabolism / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology; D005260:Female; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D014226:Triazenes / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism*
D005029:Ethylenediamines; D016328:NF-kappa B; D014226:Triazenes; C008848:1-phenyl-3,3-dimethyltriazene; D007464:Clioquinol; D051057:Proto-Oncogene Proteins c-akt; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine