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.