Interaction of cytosine arabinoside and lovastatin in human leukemia cells

Cytosine arabinoside (ara-C) is widely used for the treatment of leukemias and displays significant toxicities. Lovastatin, an HMG-CoA reductase inhib itor, is extensively used to treat hypercholesterolemia. To determine wheth er lovastatin could augment ara-C's activity we have examined their effects in the human erythroleukemia K562 cell line and the ara-C resistant ARAC8D cell line. A synergistic interaction between the two drugs was found. We h ave demonstrated that the interaction does not occur at the level of RAS bu t may involve lovastatin's effect of downregulating MAPK activity and preve nting ara-C-induced MAPK activation. These studies represent the first desc ription of a potentially beneficial interaction between lovastatin and ara- C that could be applied to the treatment of human leukemia. (C) 2001 Elsevi er Science Ireland Ltd. All rights reserved.