title: Modulation of induced cytotoxicity of doxorubicin by using apoferritin and liposomal cages.
abstract: Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin ("Apodox" and "lip-8-dox") and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. j.gumulec@gmail.com.
authors.forename: Jaromir
authors.initials: J
authors.lastname: Gumulec
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. michaelafojtu@gmail.com.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fojtu
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. 42700@mail.muni.cz.
authors.forename: Martina
authors.initials: M
authors.lastname: Raudenska
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. sztalm@med.muni.cz.
authors.forename: Marketa
authors.initials: M
authors.lastname: Sztalmachova
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. 424299@mail.muni.cz.
authors.forename: Anna
authors.initials: A
authors.lastname: Skotakova
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. vlachova.jana@centrum.cz.
authors.forename: Jana
authors.initials: J
authors.lastname: Vlachova
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. sylvie.skalickova@gmail.com.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Skalickova
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. lukasnejdl@gmail.com.
authors.forename: Lukas
authors.initials: L
authors.lastname: Nejdl
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. paulko@centrum.cz.
authors.forename: Pavel
authors.initials: P
authors.lastname: Kopel
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. l.knopfova@seznam.cz.
authors.forename: Lucia
authors.initials: L
authors.lastname: Knopfova
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. vojtech.adam@mendelu.cz.
authors.forename: Vojtech
authors.initials: V
authors.lastname: Adam
authors.affiliation: Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic. kizek@sci.muni.cz.
authors.forename: Rene
authors.initials: R
authors.lastname: Kizek
authors.affiliation: Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-12840 Prague 2, Czech Republic. stiborov@natur.cuni.cz.
authors.forename: Marie
authors.initials: M
authors.lastname: Stiborova
authors.affiliation: Department of Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. babula@med.muni.cz.
authors.forename: Petr
authors.initials: P
authors.lastname: Babula
authors.affiliation: Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic. masarik@med.muni.cz.
authors.forename: Michal
authors.initials: M
authors.lastname: Masarik
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D001052:Apoferritins; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D004337:Drug Carriers; D004339:Drug Compounding; D006736:Horses; D006801:Humans; D020128:Inhibitory Concentration 50; D008081:Liposomes
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin; D001052:Apoferritins