Desferrioxamine-caffeine shows improved efficacy in chelating iron and depleting cancer stem cells.

J Trace Elem Med Biol

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Published: March 2019

Iron chelation has already been proposed to be a feasible strategy for cancer therapeutics in that reinforced iron demand is demonstrated in cancer cells, and quite a few iron chelators have been developed for this purpose. Desferrioxamine (DFO), an iron chelator approved by the U.S. Food and Drug Administration (FDA), has been extensively examined to remove extra iron. However, DFO has been found to harbor limited efficacies in combating cancer cells due to poor cellular permeability. In the current study, we synthesized the DFO derivative, named as desferrioxamine-caffeine dimer (DFCAF) by linking DFO to caffeine with high purity and excellent stability. Our data showed that DFCAF displayed greater cellular permeability to chelate intracellular iron in 4T1 breast cancer cells than DFO, posing more inhibition on cell growth and cellular motility/invasion. Importantly, DFCAF was uncovered to remarkably deplete cancer stem cells (CSCs), as characterized by the remarkable decrease of the CD44/CD24 and ALDH subpopulation. In parallel, DFCAF was also found to greatly reverse epithelial-mesenchymal transition (EMT), suggesting the potential application to restrain tumor progression and metastasis. Collectively, these data unveiled the improved efficacy to target cancer cells and to deplete CSCs, thus opening a new path for better cancer therapeutics through iron chelation.

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http://dx.doi.org/10.1016/j.jtemb.2019.01.004DOI Listing

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