DNA adduct formation by the anticancer drug ellipticine in human leukemia HL-60 and CCRF-CEM cells.

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 (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.

• Authors: Jitka Poljaková, Eva Frei, Jacobo E Gomez, Dagmar Aimová, Tomás Eckschlager, Jan Hrabeta, Marie Stiborová
• Journal: Cancer letters (Cancer Lett) Vol. 252 Issue 2 Pg. 270-9 (Jul 18 2007) ISSN: 0304-3835 [Print] Ireland
• PMID: 17306925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• DNA Adducts
• Ellipticines
• ellipticine

Topics

• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• DNA Adducts (biosynthesis)
• Ellipticines (pharmacology)
• Humans
• Leukemia (pathology)