Combined effects of artemisinin and quinoline derivatives on mammalian cell growth and differentiation

Artemisinin derivatives are widely used in combination with quinolines and antifolates antimalarials, thanks to their high activity and safety (WHO 2001). However, animal studies reveal that artemisinins are not recommended during pregnancy. There are data indicating that embryo toxicity is due to inhibition of angiogenesis and erythropoiesis in fetal rats (Longo M. Reproductive toxicology 2006). Information about quinolines effects on human fetus are still lacking and therefore drug administrations have been avoided during gestation. (Thomas F. Lancet 2004). ln order to study the combination of artemisinin and quinoline derivatives on growing fetus, we investigated the effect of these drug associations on three different cell lines representing a possible target for toxicity: myeloid leukemia cell line (K562), microvascular endothelial cells (HMEC-1) and mouse fibrosarcoma cells (WEHI). The cytotoxic effect of the Dihydroartemisinin (DHA) and Amodiaquine (AQ) in association is less evident than the two drugs alone. The isobolograms showed an antagonistic effect of AQ toward DHA on all cell lines, revealing that probably there is a competition on the viability cell process. These results will be discussed together with the effects of the same drug combination tested on P. falciparum parasites in vitro