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- W2038286377 abstract "Introduction: Deprivation of cellular iron (Fe) may represent a novel and effective anti-cancer strategy1. Our laboratory has developed iron chelators with marked and selective anti-tumor activity against a variety of tumor types in vitro and in vivo. One of our leading compounds, Dp44mT, demonstrated potent anti-tumor activity against drug-resistant cell lines1,2 over-expressing P-gp and MRP1. Moreover, these compounds possess high activity at releasing cellular 59Fe3. Aims: To further understand the mechanism of chelator-mediated cellular 59Fe release we investigated: The difference in iron efflux between drug-resistant MCF7-VP (MRP1 hyper-expressing) cells and their wild-type counterparts (MCF7); Whether chelator-mediated Fe release was MRP1 and/or GSH-dependent and; If chelator-mediated cellular Fe release was temperature-dependent. Results: These studies demonstrated that MRP1 over-expressing MCF7-VP cells showed reduced chelator-mediated59Fe release compared to MCF-7 cells (P Interestingly, MCF7-VP cells showed higher 59Fe uptake from 59Fe-transferrin than wild-type cells. This was due to marked transferrin receptor-1 expression in MCF7-VP compared to MCF7 cells. Additionally, the only known Fe efflux pump, ferroportin1, was down-regulated in MCF7-VP cells. This latter observation was intriguing as chelator-mediated Fe efflux was depressed in this cell type. These studies indicate that chelator-mediated 59Fe release is temperature-dependent and MRP-independent. Further studies will examine the role of MRP1 in Fe uptake and metabolism. References: 1. Whitnall, M., Howard, J., Ponka, P., and Richardson, D. R., Proc Natl Acad Sci U S A103 (40), 14901 (2006). 2. Richardson, D. R. and Milnes, K., Blood89 (8), 3025 (1997). 3. Richardson, D. R., Biochim Biophys Acta1320 (1), 45 (1997). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr C40." @default.
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- W2038286377 date "2011-11-12" @default.
- W2038286377 modified "2023-09-25" @default.
- W2038286377 title "Abstract C40: Understanding the mechanism of action of novel iron chelators on drug-resistant neoplastic cells." @default.
- W2038286377 doi "https://doi.org/10.1158/1535-7163.targ-11-c40" @default.
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