Biochemical effects of ellipticine on leukemia L1210 cells

Abstract

Ellipticine, a plant alkaloid, is cytotoxic to L1210 cells growing in culture and the growth inhibition cannot be prevented or reversed by the simultaneous addition of several metabolite mixtures. Furthermore, the inhibition cannot be eliminated by the removal of drug after a contact period of 15–120 min with cells and the phenomenon is dose related. Ellipticine significantly inhibits DNA, RNA and protein synthesis and as was found with the inhibition of cell growth, the inhibition was not reversible by removal of drug. Ellipticine shows no apparent effect on thymidine and uridine kinases nor on RNA polymerase, but it markedly inhibits DNA polymerase activity. With partially purified DNA polymerases of L1210 cells and of Micrococcus lysodeikticus, the inhibition by ellipticine varied with the DNA templates used, e.g. salmon sperm DNA, poly[d(A-T) and poly(dG) · poly(dC). Ellipticine was found to interact with DNA, RNA and proteins. These results collectively suggest that the interaction with macromolecules is one of the primary determinants of the action of ellipticine against L1210 leukemia. The inhibitory effects of methoxy-9-ellipticine on L1210 cell growth and macromolecule synthesis are comparable to those of ellipticine.