title: Modulation of iron metabolism by iron chelation regulates intracellular calcium and increases sensitivity to doxorubicin.
abstract: 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.
authors.affiliation: Istanbul University. lemany@istanbul.edu.tr.
authors.forename: Leman
authors.initials: L
authors.lastname: Yalcintepe
authors.forename: Emre
authors.initials: E
authors.lastname: Halis
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism; D003676:Deferoxamine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry*; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry*; D020014:K562 Cells; D009369:Neoplasms / Q000378:metabolism; D017382:Reactive Oxygen Species; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D007501:Iron; D003676:Deferoxamine; D002118:Calcium