1. Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors.
- Author
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Denel-Bobrowska M, Łukawska M, Rogalska A, Forma E, Bryś M, Oszczapowicz I, and Marczak A
- Subjects
- Apoptosis drug effects, Apoptosis genetics, Cell Line, Tumor, Cell Proliferation drug effects, Comet Assay, DNA Damage, Humans, Anthracyclines pharmacology, Neoplasms pathology
- 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., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
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