title: Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors.
abstract: Oxazolinodoxorubicin (O-DOX) and oxazolinodaunorubicin (O-DAU) are novel anthracycline derivatives with a modified daunosamine moiety. In the present study, we evaluated the cytotoxicities, genotoxicities and abilities of O-DOX and O-DAU to induce apoptosis in cancer cell lines (SKOV-3; A549; HepG2), and compared the results with their parent drugs. We assessed antiproliferative activity by MTT assay. We evaluated apoptosis-inducing ability by double-staining with fluorescent probes (Hoechst 33258/propidium iodide), and by determining expression levels of genes involved in programmed cell death by reverse transcription-polymerase chain reaction. Genotoxicities of the compounds were tested by comet assays. Oxazolinoanthracyclines demonstrated high anti-tumor activity. O-DOX had significantly higher cytotoxicity, apoptosis-inducing ability, and genotoxicity compared with parental doxorubicin (DOX) in all tested conditions, while O-DAU activity differed among cell lines. The mechanism of oxazoline analog action appeared to involve the mitochondrial pathway of programmed cell death. These results provide further information about oxazoline derivatives of commonly used anthracycline chemotherapy agents. O-DOX and O-DAU have the ability to induce apoptosis in tumor cells.
authors: Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. Electronic address: mdenel@biol.uni.lodz.pl.
authors: Marta
authors: M
authors: Denel-Bobrowska
authors: Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw, Poland.
authors: Małgorzata
authors: M
authors: Łukawska
authors: Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors: Aneta
authors: A
authors: Rogalska
authors: Department of Cytobiochemistry, Institute of Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors: Ewa
authors: E
authors: Forma
authors: Department of Cytobiochemistry, Institute of Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors: Magdalena
authors: M
authors: Bryś
authors: Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw, Poland.
authors: Irena
authors: I
authors: Oszczapowicz
authors: Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors: Agnieszka
authors: A
authors: Marczak
mesh_terms: D018943:Anthracyclines / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage; D006801:Humans; D009369:Neoplasms / Q000473:pathology*
chemical_list: D018943:Anthracyclines
keywords: Anticancer drug; Apoptosis; Cytotoxicity; Necrosis; Oxazolinoanthracycline