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Inhibitory Activity of Iron Chelators ATA and DFO on MCF-7 Breast Cancer Cells and Phosphatases PTP1B and SHP2.

Anticancer research (2017-09-06)
Alicja Kuban-Jankowska, Kamlesh K Sahu, Magdalena Gorska-Ponikowska, Jack A Tuszynski, Michal Wozniak
RESUMEN

Rapidly-dividing cancer cells have higher requirement for iron compared to non-transformed cells, making iron chelating a potential anticancer strategy. In the present study we compared the anticancer activity of uncommon iron chelator aurintricarboxylic acid (ATA) with the known deferoxamine (DFO). We investigated the impact of ATA and DFO on the viability and proliferation of MCF-7 cancer cells. Moreover we performed enzymatic activity assays and computational analysis of the ATA and DFO effects on pro-oncogenic phosphatases PTP1B and SHP2. ATA and DFO decrease the viability and proliferation of breast cancer cells, but only ATA considerably reduces the activity of PTP1B and SHP2 phosphatases. Our studies indicated that ATA strongly inactivates and binds in the PTP1B and SHP2 active site, interacting with arginine residue essential for enzyme activity. We confirmed that iron chelating can be considered as a potential strategy for the adjunctive treatment of breast cancer.

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Sigma-Aldrich
Aurintricarboxylic acid, practical grade, ≥85% (titration), powder
Sigma-Aldrich
PTP1B full length Active human, recombinant, expressed in E. coli, aqueous solution, ≥55% (SDS-PAGE)