Statins induce lethal effects in acute myeloblastic leukemia [corrected] cells within 72 hours.
HMG-CoA Reductase inhibitors (statins) induce apoptosis in acute myeloid leukemia (AML) cells in vitro; however, the concentrations associated with cell death in AML cells are higher than those clinically tolerated during prolonged therapy. We therefore wished to determine whether short exposures to lovastatin might induce cell death in AML cells at clinically attainable concentrations. The time and concentration dependence of HL60 and U937 cells was determined and showed that cell death was delayed. IC(50) values and IC(90) values determined on day 6 suggested that the sensitivity of AML cells to statins may occur at lower concentrations than previously reported. After 72 h, mevalonate did not rescue AML cells from cytotoxic concentrations of statins, suggesting that, although cell death was delayed, lovastatin induced lethal effects within 72 h. In conjunction with previously reported Phase I studies, the data presented here suggest that the high-dose, short course statins may be useful for the treatment of patients with AML.
Burke
Lillian P
LP
Department of Internal Medicine, Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA.
Kukoly
Cynthia A
CA
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D008798:Mevalonic Acid