Publication at Faculty of Science, Second Faculty of Medicine |
2007
Abstract
Ellipticine induces formation of two DNA adducts in leukemia HL-60 and CCRF-CEM cells, identical with deoxyguanosine adducts generated by ellipticine metabolites 13-hydroxyellipticine and 12-hydroxyellipticine in vitro and in vivo. The ellipticine cytotoxicity to HL-60 (IC50 = 0.64 mu M) and CCRF-CEM cells (IC50 = 4.7 mu M) correlates with levels of DNA adducts.
The different expressions of enzymes activating ellipticine in cells explain this finding. While cytochrome P450 1A1 and cyclooxygenase-1 are expressed in both cells, HL-60 cells express also high levels of another activator, myeloperoxidase.
The results suggest the adduct formation as a new mode of antitumor action of ellipticine for leukemia.