DNA adduct formation by the anticancer drug ellipticine in human leukemia HL-60 and CCRF-CEM cells.
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 (IC(50)=0.64microM) and CCRF-CEM cells (IC(50)=4.7microM) 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.
Poljaková
Jitka
J
Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, 128 40 Prague 2, Czech Republic.
Frei
Eva
E
Gomez
Jacobo E
JE
Aimová
Dagmar
D
Eckschlager
Tomás
T
Hrabeta
Jan
J
Stiborová
Marie
M
D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018736:DNA Adducts / Q000096:biosynthesis*; D004611:Ellipticines / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000473:pathology*
D000970:Antineoplastic Agents; D018736:DNA Adducts; D004611:Ellipticines; C034192:ellipticine