Iron Chelation Enhances TAM and Triple-Negative Breast Cancer Cell Death

Abstract

The goal of this study is to complete preclinical testing of Deferiprone (DFP), an iron chelator in clinical use for non-oncologic diseases. To date we have demonstrated that DFP has an IC50 for TNBC within the range achieved after a clinical dose, and enhances the effect of taxol in 4T1 tumors. The IC50 for tumor cells was lower than measured for macrophages (M0, M1, M2) indicating potential therapeutic gain and safety in treating cancer cells. In 4T1 tumors, DFP did not change iron concentration measured in tissues (spleen and tumor). In perfused 4T1 cells, we demonstrated metabolic inhibition of the tricarboxylic acid cycle and lipid metabolism by DFP and similar studies are ongoing in the MDA-231. We have measured lactate in tumors (control and DFP treated) and the data are currently undergoing analysis.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2019
Accession Number
AD1096136

Entities

People

  • Jason A Koutcher
  • Ronald Blasberg

Organizations

  • Sloan-Kettering Institute

Tags

DTIC Thesaurus Topics

  • Acquisition
  • Breast Cancer
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chelation
  • Chemical Synthesis
  • Chemistry
  • Diseases And Disorders
  • Inhibition
  • Macrophages
  • Magnetic Resonance
  • Metabolism
  • Neoplasms
  • New York
  • Statistical Analysis
  • Tissues

Fields of Study

  • Medicine

Readers

  • Analytical Chemistry
  • Medical Imaging.
  • Oncology (Cancer Research).