Aclarubicin in subtoxic doses reduces doxorubicin cytotoxicity in human non-small cell lung adenocarcinoma (A549) and human hepatocellular carcinoma (HepG2) cells by decreasing DNA damage

• Published in: Toxicology in vitro 2019-03, Vol.55, p.140-150
• Main Authors: Gajek, Arkadiusz, Rogalska, Aneta, Koceva-Chyła, Aneta
• Format: Article
• Language: English
• Subjects: A549 Cells; Aclarubicin; Aclarubicin - pharmacology; Acridine; Adenocarcinoma; Anthracycline; Antibiotics, Antineoplastic - pharmacology; Apoptosis; Biotechnology; Cancer; Cell cycle; Cell Cycle - drug effects; Cell Survival - drug effects; Cytotoxicity; Damage; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; Doxorubicin; Doxorubicin - pharmacology; Drugs; Ethidium bromide; G1 phase; Genotoxicity; Hep G2 Cells; Hepatocellular carcinoma; Hepatocytes; Humans; Liver; Liver cancer; Lungs; Modulation of cytotoxicity; Toxicity; Tumor cell lines; Verapamil
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2018.12.015

In the study, the cytotoxicity and genotoxicity of aclarubicin (ACL) against A549 (human non-small cell lung adenocarcinoma) and HepG2 (human hepatocellular carcinoma) cell lines were evaluated and compared with that of doxorubicin (DOX). The effect of both anthracyclines in combination was also investigated. In order to get a deeper insight into the effectiveness of the drugs and their combination, their effects on the DNA damage and distribution of the cell cycle of A549 and HepG2 cells were investigated. After treatment with investigated compounds, apoptotic and necrotic morphological changes were estimated by double staining cells with orange acridine and ethidium bromide. The results showed that ACL was much more cytotoxic against lung (A549) and liver (HepG2) cancer cell lines than DOX. However, the drugs affected the cell cycle differently. ACL arrested cells in the G1 phase, while DOX arrested them in the G2/M phase. DOX and ACL at high concentrations are able to trigger apoptosis in both A549 and HepG2 cells. When the drugs were used in combination, subtoxic concentrations of ACL antagonized the cytotoxic effects of doxorubicin. Pre-incubation of cells with subtoxic concentrations of ACL reduced the level of DNA damage by DOX but increased DOX genotoxicity in the presence of verapamil. [Display omitted] •Subtoxic concentrations of ACL antagonized the cytotoxic effects of DOX.•Subtoxic concentrations of ACL reduced the DOX genotoxicity.•ACL is revealed as a negative cytotoxicity modulator of DOX.