Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin

  • Leman Yalcintepe Istanbul University
  • Emre Halis Istanbul University
Keywords: Intracellular calcium, iron uptake, doxorubicin, desferrioxamine


Increased intracellular iron levels can both promote cell proliferation and death, as such; iron has a “two-sided effect” in the delicate balance of human health. Though the role of iron in the development of cancer remains unclear, investigations of iron chelators as anti-tumor agents have revealed promising results. Here, we investigated the influence of iron and desferrioxamine (DFO), the iron chelating agent on intracellular calcium in a human leukemia cell line, K562. Iron uptake is associated with increased reactive oxygen species (ROS) generation. Therefore, we showed that iron also caused dose-dependent ROS generation in K562 cells. The measurement of intracellular calcium was determined using Furo-2 with a fluorescence spectrophotometer. The iron delivery process to the cytoplasmic iron pool was examined by monitoring the fluorescence of cells loaded with calcein-acetoxymethyl. Our data showed that iron increased intracellular calcium, and this response was 8 times higher when cells were incubated with DFO. K562 cells with DFO caused a 3.5 times increase of intracellular calcium in the presence of doxorubicin (DOX). In conclusion, DFO induces intracellular calcium and increases their sensitivity to DOX, a chemotherapeutic agent.


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Author Biographies

Leman Yalcintepe, Istanbul University
Department of Biophysics
Emre Halis, Istanbul University
Department of Biophysics


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Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin
How to Cite
Yalcintepe L, Halis E. Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin. Bosn J of Basic Med Sci [Internet]. 2016Jan.1 [cited 2020Aug.10];16(1):14-0. Available from: