Synergistic antiproliferative activity of tumor necrosis factor alpha (TNF-α) and lovastatin

We assessed the antiproliferative effect of tumor necrosis factor alpha (TNF-α) and lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, alone and in combination, on two murine tumor cell lines. Recombinant TNF-α inhibited proliferation of murine MmB16 melanoma cells in a concentration-dependent fashion but stimulated growth of murine L1210 leukemia cells at 0.1 ng/ml concentration. Lovastatin inhibited proliferation both of murine MmB16 melanoma cells and of murine L1210 leukemia cells in a concentration-dependent fashion. In combination with tumor necrosis factor alpha lovastatin inhibited synergistically growth of both cell lines as assessed by isobologram analysis. Our data show that lovastatin, a cholesterol synthesis inhibitor, introduced to the clinic to treat hyercholesterolemia, used either as a single agent or in combination with TNF-α inhibits growth of MmB16 melanoma and L1210 leukemia cells.