Identification of the key pathway of oxazolinoanthracyclines mechanism of action in cells derived from human solid tumors

Journal Article · Thu Dec 15 04:00:00 EST 2016 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/J.TAAP.2016.10.018· OSTI ID:22690881

Denel-Bobrowska, Marta ^[1]; Łukawska, Małgorzata ^[2]; Rogalska, Aneta ^[1]; Forma, Ewa; Bryś, Magdalena ^[3]; Oszczapowicz, Irena ^[2]; Marczak, Agnieszka ^[1]

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1. Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland)
2. Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska St., 02-516 Warsaw (Poland)
3. Department of Cytobiochemistry, Institute of Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz (Poland)

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. - Highlights: • Substituted amino group increased the anticancer activity of anthracyclines. • Mitochondrial apoptotic pathway seems to be involved in the mechanism of action. • Favorable biological properties of oxazoline derivatives were confirmed.

• OSTI ID: 22690881
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Vol. 313; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADP
APOPTOSIS
BORON CHLORIDES
BROMIDES
CATTLE
CHAIN REACTIONS
CHEMOTHERAPY
CYTOCHROMES
DOXORUBICIN
FLUORESCENCE
HEPATOMAS
HYPOXANTHINE
HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE
IODIDES
LYMPHOMAS
MITOCHONDRIA
NECROSIS
PHOSPHOTRANSFERASES
POLYMERASE CHAIN REACTION
POLYMERASES
RECEPTORS
RIBOSE
TOXICITY
TRANSCRIPTION
TUMOR CELLS