title: Doxorubicin-transferrin conjugate triggers pro-oxidative disorders in solid tumor cells.
abstract: The formation of reactive oxygen species (ROS) is a widely accepted mechanism of doxorubicin (DOX) toxicity toward cancer cells. However, little is known about the potential of new systems, designed for more efficient and targeted doxorubicin delivery (i.e. protein conjugates, polymeric micelles, liposomes, monoclonal antibodies), to induce oxidative stress (OS) in tumors and hematological malignancies. Therefore, the objective of our study was to determine the relation between the toxicity of doxorubicin-transferring (DOX-TRF) conjugate and its capability to generate oxidative/nitrosative stress in solid tumor cells. Our research proves that DOX-TRF conjugate displays higher cytotoxicity towards lung adenocarcinoma epithelial (A549) and hepatocellular carcinoma (HepG2) cell lines than the reference free drug (DOX) and induces more extensive OS, characterized by a significant decrease in the total cellular antioxidant capacity, glutathione level and amount of -SH groups and an increase in hydroperoxide content. The intracellular redox imbalance was accompanied by changes in the transcription of genes encoding key antioxidant enzymes engaged in the sustaining of cellular redox homeostasis: superoxide dismutase (SOD), catalase (CAT), glutathione transferase (GST) and glutathione peroxidase (GP).
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland. Electronic address: szwedma@biol.uni.lodz.pl.
authors.forename: Marzena
authors.initials: M
authors.lastname: Szwed
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland. Electronic address: dominikawrona1@wp.pl.
authors.forename: Dominika
authors.initials: D
authors.lastname: Wrona
authors.affiliation: Laboratory of Transcriptional Regulation, Institute of Medical Biology, PAS, Lodowa St. 106, 93-232 Lodz, Poland. Electronic address: kkania@cbm.pan.pl.
authors.forename: Katarzyna D
authors.initials: KD
authors.lastname: Kania
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland. Electronic address: koceva@biol.uni.lodz.pl.
authors.forename: Aneta
authors.initials: A
authors.lastname: Koceva-Chyla
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska St. 141/143, 90-236 Lodz, Poland. Electronic address: aszwar@biol.uni.lodz.pl.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Marczak
mesh_terms: D002374:Catalase / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D014168:Transferrin / Q000494:pharmacology*
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014168:Transferrin; C000599870:doxorubicin-transferrin conjugate; D004317:Doxorubicin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione
keywords: Antioxidant enzymes; Doxorubicin–transferrin conjugate; Glutathione level; Oxidative stress