Journal article
Desferri-exochelin induces death by apoptosis in human breast cancer cells but does not kill normal breast cells
Breast cancer research and treatment, Vol.69(1), pp.69-79
09/2001
DOI: 10.1023/A:1012211828319
PMID: 11759830
Abstract
A major goal of cancer chemotherapy is the identification of cytotoxic compounds that are highly selective for cancer cells. We describe here one such compound – a novel iron chelator, desferri-exochelin 772SM. This desferri-exochelin has unique chemical and pharmacological properties, including extremely high iron binding affinity, the capacity to block iron-mediated redox reactions, and lipid solubility which enables it to enter cells rapidly. At low concentrations, this desferri-exochelin kills T47D-YB and MCF-7 human breast cancer cells by inducing apoptosis, but only reversibly arrests the growth of normal human mammary epithelial cells without cytotoxicity. Since iron-loaded exochelin is ineffective, iron chelation accounts for the efficacy of desferri-exochelin. For both the killing of breast cancer cells and the growth arrest of normal breast epithelial cells, desferri-exochelin was effective at much lower concentrations than the lipid-insoluble iron chelator deferoxamine, which has shown only limited potential as an anti-cancer agent. Growth arrest of progesterone receptor positive T47D-YB cells with the progestin R5020 transiently protects them from the cytotoxic effects of desferri-exochelin, but the cells are killed after cell growth resumes. Similarly, MCF-7 cells arrested with the estrogen antagonist ICI182780 are transiently resistant to killing by desferri-exochelin. Thus the desferri-exochelin is cytotoxic only to actively growing tumor cells. Since desferri-exochelin 772SM can selectively and efficiently destroy proliferating cancer cells without damaging normal cells, it may prove useful for the treatment of cancer.
Details
- Title: Subtitle
- Desferri-exochelin induces death by apoptosis in human breast cancer cells but does not kill normal breast cells
- Creators
- Paula M. B Pahl - University of Colorado HealthMarcus A Horwitz - University of California, Los AngelesKathryn B Horwitz - University of Colorado HealthLawrence D Horwitz - University of Colorado Health
- Resource Type
- Journal article
- Publication Details
- Breast cancer research and treatment, Vol.69(1), pp.69-79
- DOI
- 10.1023/A:1012211828319
- PMID
- 11759830
- NLM abbreviation
- Breast Cancer Res Treat
- ISSN
- 0167-6806
- eISSN
- 1573-7217
- Publisher
- Springer
- Language
- English
- Date published
- 09/2001
- Academic Unit
- Cardiovascular Medicine; Obstetrics and Gynecology; Internal Medicine
- Record Identifier
- 9984656538902771
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