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Simvastatin, an inhibitor of cholesterol biosynthesis, shows a synergistic effect with N,N'-bis(2-chloroethyl)-N-nitrosourea and beta-interferon on human glioma cells.
Soma, M R; Pagliarini, P; Butti, G; Paoletti, R; Paoletti, P; Fumagalli, R.
Affiliation
  • Soma MR; Institute of Pharmacological Sciences, University of Milan, Italy.
Cancer Res ; 52(16): 4348-55, 1992 Aug 15.
Article in En | MEDLINE | ID: mdl-1643632
ABSTRACT
The effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on human glioma cell growth was investigated. When incubated with simvastatin, cell proliferation decreased in a concentration-dependent fashion, as measured by cell number and [3H]-thymidine incorporation into DNA (concentration producing 50% inhibition, 60 nM). The effect was detectable 12 h after cells were exposed to the drug and persisted for 2 days. Addition of mevalonate to cells exposed effect of simvastatin in combination with beta-interferon and N,N'-bis(2-chloroethyl)-N-nitrosourea, both antitumoral drugs, was also evaluated by cell growth inhibition assay. The concentration producing 50% inhibition for each of these drugs was 650 units/ml and 50 nM, respectively. Subliminal concentrations of beta-interferon or N,N'-bis(2-chloroethyl)-N-nitrosourea were incubated together with 1 nM simvastatin. The data were analyzed with the aid of an isobologram using the concept of an envelope of additivity. Simultaneous cell exposure to simvastatin with either N,N'-bis(2-chloroethyl)-N-nitrosourea or beta-interferon produced a strong synergistic inhibitory effect on cell proliferation. These data provide in vitro support for the possibility that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, utilized as plasma cholesterol-lowering agents, could potentiate the effect of antiblastic drugs on tumor growth.
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Collection: 01-internacional Database: MEDLINE Main subject: Lovastatin / Glioma / Hydroxymethylglutaryl CoA Reductases / Anticholesteremic Agents Limits: Humans Language: En Journal: Cancer Res Year: 1992 Document type: Article Affiliation country: Italia
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Collection: 01-internacional Database: MEDLINE Main subject: Lovastatin / Glioma / Hydroxymethylglutaryl CoA Reductases / Anticholesteremic Agents Limits: Humans Language: En Journal: Cancer Res Year: 1992 Document type: Article Affiliation country: Italia