title: Assessment of pro-apoptotic activity of doxorubicin-transferrin conjugate in cells derived from human solid tumors.
abstract: Conjugates of anthracyclines are a new possibility for anticancer agent delivery, which seems to be a very promising alternative to the currently used cancer treatment strategies. In our study, we investigated the ability of a doxorubicin-transferrin (DOX-TRF) conjugate to induce cell death in two solid tumor cell lines: non-small cell lung cancer (A549) and hepatocellular liver carcinoma (HepG2). The observed effects of the DOX-TRF conjugate on these cell cultures were compared with those of free doxorubicin (DOX), a widely used antineoplastic therapeutic agent. Our results provided direct evidence that the investigated conjugate is considerably more cytotoxic to the examined human cancer cell lines than is DOX alone. Moreover, we confirmed that the antitumor efficacy of DOX-TRF conjugate is related to its apoptosis-inducing ability, which was shown during measurements of typical features of programmed cell death. In solid tumor cell lines, the DOX-TRF conjugate induced changes in cellular morphology, mitochondrial membrane potential and caspases-3 and -9 activities. Furthermore, all of the analyzed hallmarks of apoptosis were confirmed by the oligonucleosomal DNA fragmentation assay and by a real-time PCR quantitative study, which displayed the superiority of the conjugate-induced programmed cell death over free drug-triggered cell death.
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, Poland. Electronic address: szwedma@biol.uni.lodz.pl.
authors.forename: Marzena
authors.initials: M
authors.lastname: Szwed
authors.affiliation: Laboratory of Transcriptional Regulation, Institute for Medical Biology, PAS, Lodowa 106 Street, 93-232 Lodz, Poland. Electronic address: kkania@cbm.pan.pl.
authors.forename: Katarzyna Dominika
authors.initials: KD
authors.lastname: Kania
authors.affiliation: Department of Thermobiology, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Street, 90-236 Lodz, Poland. Electronic address: zjozwiak@biol.uni.lodz.pl.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Jozwiak
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051033:Apoptosis Inducing Factor / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014168:Transferrin / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494829:AIFM1 protein, human; D000970:Antineoplastic Agents; D051033:Apoptosis Inducing Factor; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014168:Transferrin; D051028:bcl-2-Associated X Protein; C000599870:doxorubicin-transferrin conjugate; D004317:Doxorubicin; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D002154:Calpain; D053148:Caspase 3; D053453:Caspase 9; C484806:CAPN1 protein, human
keywords: Anthracyclines; Drug delivery systems; Solid tumors; Transferrin