Synergistic antiproliferative activity of tumor necrosis factor alpha (TNF-alpha) and lovastatin.
We assessed the antiproliferative effect of tumor necrosis factor alpha (TNF-alpha) 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-alpha 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 hypercholesterolemia, used either as a single or in combination with TNF-alpha inhibits growth of MmB16 melanoma and L1210 leukemia cells.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D034882:Lamins; D007939:Leukemia L1210 / Q000473:pathology; D008148:Lovastatin / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000473:pathology; D051379:Mice; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D018631:ras Proteins / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D034882:Lamins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008148:Lovastatin; D018631:ras Proteins