Lovastatin induces growth inhibition and apoptosis in human malignant glioma cells.
The competitive HMG-CoA reductase inhibitor lovastatin has been shown to suppress growth and induce morphological changes in a variety of non-glioma tumor cell lines. This study assesses the effects of this agent on the growth and survival of the human malignant glioma cell lines A172 and U87-MG. The response to the drug was investigated using a cell proliferation assay which revealed significant dose-dependent growth inhibition. Treatment with as little as 100 nM lovastatin over a period of 72 hours led to DNA degradation into nucleosome-sized fragments characteristic of apoptosis. Our data suggest that HMG-CoA reductase inhibitors such as lovastatin merit further investigation as potential therapeutic agents for the treatment of malignant gliomas.
Jones
K D
KD
Department of Neurological Surgery, University of Southern California School of Medicine, Los Angeles 90033.
Couldwell
W T
WT
Hinton
D R
DR
Su
Y
Y
He
S
S
Anker
L
L
Law
R E
RE
D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D017368:Protein Prenylation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D008148:Lovastatin