title: Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired resistance to doxorubicin and cisplatin.
abstract: The development of resistance of cancer cells to therapeutic agents is the major obstacle in the successful treatment of breast cancer and the main cause of breast cancer recurrence. The results of several studies have demonstrated an important role of altered cellular iron metabolism in the progression of breast cancer and suggested that iron metabolism may be involved in the acquisition of a cancer cell drug-resistant phenotype. In the present study, we show that human MCF-7 breast cancer cells with an acquired resistance to the chemotherapeutic drugs doxorubicin (MCF-7/DOX) and cisplatin (MCF-7/CDDP) exhibited substantial alterations in the intracellular iron content and levels of iron-regulatory proteins involved in the cellular uptake, storage and export of iron, especially in profoundly increased levels of ferritin light chain (FTL) protein. The increased levels of FTL in breast cancer indicate that FTL may be used as a diagnostic and prognostic marker for breast cancer. Additionally, we demonstrate that targeted downregulation of FTL protein by the microRNA miR-133a increases sensitivity of MCF-7/DOX and MCF-7/CDDP cells to doxorubicin and cisplatin. These results suggest that correction of iron metabolism abnormalities may substantially improve the efficiency of breast cancer treatment.
authors: Department of Mechanisms of Anticancer Therapy, R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, Kiev, Ukraine.
authors: Vasyl F
authors: VF
authors: Chekhun
authors: Natalia Yu
authors: NY
authors: Lukyanova
authors: Capital A Cyrillicnatoliy P
authors: CA
authors: Burlaka
authors: Natalia A
authors: NA
authors: Bezdenezhnykh
authors: Svitlana I
authors: SI
authors: Shpyleva
authors: Volodymyr P
authors: VP
authors: Tryndyak
authors: Frederick A
authors: FA
authors: Beland
authors: Igor P
authors: IP
authors: Pogribny
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D001052:Apoferritins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D002945:Cisplatin / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D007501:Iron / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; C507433:FTL protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D004317:Doxorubicin; D001052:Apoferritins; D007501:Iron; D002945:Cisplatin