SEARCH · Search PubMed

Results for “Mevalonic Acid”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed1976

[Effect of vitamin E on the alteration of the cholesterol metabolism with the aging of mice (author's transl)].

1. Vitamin E (alpha-tochopherol acetate) 200 mg/kg was injected twelve times every five days into two groups of dd mice, one six months old and the other one month old. Thereafter the incorporation of acetate-1-14C or mevalonic acid-2-14C into sterols in the liver and kidney was examined. (1) In the liver, the incorporation of acetate-14C or mevalonic acid -14C into total lipid, total cholesterol, total fatty acid and proteins was lower in the old group than in the young group. When vitamin E was administered to the young group, hepatic cholesterol biosynthesis from the acetate-1-14C was reduced while total lipids, total fatty acid and proteins were not affected. Whereas when vitamin E was administered to the old group, the body weight increased, the hepatic cholesterol was reduced and the incorporation of acetate-1-14C into total lipids and proteins was increased while that into total cholesterol was reduced, and that into total fatty acid was not affected. The cholesterol biosynthesis was inhibited at the step of conversion of acetate to mevalonic acid in both young and old groups by the injection of vitamin E. (2) In the kidney the incorporation of acetate-1-14C into total lipid, total fatty acid and total cholesterol was more reduced in the old group of mice than in the young group. The administration of vitamin E to the young group of mice reduced the incorporation of acetate-1-14C into total lipid, total fatty acid and total cholesterol, while in the old group of mice administered with vitamin E the incorporation into total lipid and total cholesterol was not affected but that into total fatty acid was increased. The incorporation of mevalonic acid-2-14C into cholesterol was reduced in the young group of mice administered with vitamin E while the same was not affected in the old group. 2. When the old group of mice was fed with a diet containing vitamin E for two months, the excretion of bile acid-14C derived from injected cholesterol4-14C or cholic acid-24-14C was increased and the disappearance of hepatic cholesterol-14C became more rapid. As a result, it may be said that aging brought about the reduction of the lipid biosynthesis in liver and kidney, which was recovered partially by the administration of vitamin E. With regard to the cholesterol metabolism, the aging increased total cholesterol level, which was adjusted by vitamin E. The effect of vitamin E appeared to depend upon the supression of cholesterol biosynthesis as well as the increase of cholesterol catabolism and the excretion of bile acid.

Acetates↗

PubMed1982

Biochemical characterization of the OXI mutants of the yeast Saccharomyces cerevisiae.

OXI mutants in Saccharomyces cerevisiae lack a functional cytochrome c oxidase. Wild type and OXI mutants were grown in the presence of radioactive delta-amino[14C]levulinic acid, a precursor of porphyrin and heme, and [3H]mevalonic acid, a precursor of the alkyl side-chain of heme a. SDS polyacrylamide gel electrophoresis of the delipidated mitochondria showed that delta-amino[14C]levulinic acid was distributed into three bands migrating in the regions of Mr 28 000, 13 500, and 10 000, while [3H]mevalonic acid was found in a single band with apparent Mr of 10 000. The immunoprecipitates obtained by incubating the solubilized mitochondria of any OXI mutant with antibodies against cytochrome c oxidase, showed, after delipidation, a high specific radioactivity due to delta-amino[14C]levulinic acid and [3H]mevalonic acid. This suggested that a prophyrin a was present in all these OXI mutants. HCl fractionation confirmed the presence of porphyrin a in the apooxidase of these mutants. Atomic absorption spectra of the immunoprecipitate of cytochrome c oxidase showed that copper was not detectable in the mutant OXI IIIa which lacked subunit 1, but was present in the mutant OXI IIIb, which exhibited a minor alteration in the electrophoretic mobility of subunit 1. In OXI I and II mutants there was a 50% reduction in the amount of copper in the immunoprecipitated cytochrome c oxidase. These observations may be interpretable as follows: (1) alterations in polypeptide biosynthesis due to the OXI mutations lead to an improper configuration of cytochrome c oxidase, so that ferrochelatase cannot transfer iron into porphyrin a; (2) subunit I is the binding site for copper, but the mutations in subunits II and III alter the binding site of one of the two copper atoms in subunit I.

Aminolevulinic Acid↗

PubMed1973

Biosynthetic studies on aromatic carotenoids. Biosynthesis of chlorobactene.

1. The incorporation of [2-(14)C]mevalonic acid by Chloropseudomonas ethylica strain 2K into chlorobactene was studied. 2. Oxidative degradation of chlorobactene of constant specific radioactivity produced labelled benzenecarboxylic acids and indicated that the benzene ring originates from mevalonic acid. 3. Decarboxylation studies demonstrated a stereospecific methyl migration in the formation of the 1,2,5-trimethylphenyl group of chlorobactene. The migrating methyl group was derived from the C-3' position of mevalonic acid.

Autoradiography↗

PubMed1976

[Studies on the mechanism of lowering of the cholesterol level by ethyl-alpha-p-chlorophenoxy-isobutyrate (clofibrate) (author's transl)].

Amimal experiments were conducted to elucidate the mechanism responsible for lowering the blood cholesterol level of mice by clofibrate (CPIB). 1. Cholesterol biosynthesis: (1) Cholesterol biosynthesis from acetate-1-14C or mevalonic acid-2-14C in liver, blood, intestine and kidney was not changed when 0.3 X 10(-3) M CPIB was added to the liver homogenate, when mice were fed on a basal diet containing 0.1% CPIB for 10 days or fed on a basal diet containing 0.5% CPIB for 18 days, and when fed on a diet containing both cholesterol and 0.5% CPIB for 10 days. (2) However, the cholesterol biosynthesis in liver and blood of the mice fed on the basal diet containing 0.5% CPIB for 10 days was suppressed at the step of conversion of acetate to mevalonic acid. In addition, since the incorporation of acetate-1-14C into squalene and of mevalonic acid-2-14C into squalene and ianosterol was suppressed in the liver homogenate of the mice, the cholesterol biosynthesis was depressed at the step of conversion of mevalonic acid to squalene. Therefore, CPIB depressed the cholesterol biosynthesis at both steps before and after mevalonic acid. 2. The fecal excretion of the sterol-14C and bile acid-14C derived from injected cholesterol -14C: When mice injected with cholesterol-14C were kept on a basal diet or cholesterol-added diet containing 0.1% CPIB, the excretion of sterol-14C and nonsaponifiable materials-14C in the feces was markedly increased in the case of basal diet as well as cholesterol-added diet. However, the excretion of total bile acid-14C was not changed when mice were fed on the basal diet, but it was markedly increased when fed on the cholesterol-added diet. The specific radioactivity of sterol-14C in blood 30 days after injection was reduced in the basal diet or the cholesterol-added diet, while that in liver was not changed or increased. Total cholesterol level in blood 30 days after injection was not affected in mice fed on basal diet and was reduced in mice fed on the cholesterol-added diet. From the above facts, the lowering effective of CPIB on the blood cholesterol level appears to depend not on the alteration of the cholesterol biosynthesis but on the increase of excretion of sterol derived from the tissue cholesterol in the feces.

Acetates↗

PubMed2002

3-hydroxy-3-methylglutaryl coenzyme A reductase-independent inhibition of CD40 expression by atorvastatin in human endothelial cells.

OBJECTIVE: 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) exert potent anti-inflammatory effects that are independent of their cholesterol-lowering action. We have investigated the effects of these drugs on cytokine-stimulated CD40 expression in human cultured endothelial cells and monocytes. METHODS AND RESULTS: Reverse transcription-polymerase chain reaction and Western blot analysis revealed that treatment of either cell type with atorvastatin, cerivastatin, or pravastatin (1 to 10 micromol/L) inhibited interferon-gamma plus tumor necrosis factor-alpha-stimulated CD40 expression by approximately 50%, an effect that was not reversed by the HMG-CoA reductase product mevalonic acid (400 micromol/L). In contrast, mevalonic acid prevented the inhibitory effect of atorvastatin on cytokine-stimulated vascular cell adhesion molecule-1 expression and subsequent adhesion of THP-1 monocytes to the cultured endothelial cells. Transcription factor analysis revealed an inhibition by atorvastatin of nuclear factor-kappaB plus signal transducer and activator of transcription-1-dependent de novo synthesis of interferon regulatory factor-1, governing cytokine-stimulated CD40 expression in these cells. One consequence of this statin-dependent downregulation of CD40 expression was a decrease in CD40 ligand-induced endothelial interleukin-12 expression. CONCLUSIONS: By interfering with cytokine-stimulated CD40 expression in vascular cells, statins thus seem capable of attenuating CD40 ligand-induced proinflammatory responses, including atherosclerosis. In addition, they point to the coexistence of HMG-CoA reductase-dependent and -independent effects of statins in the same cell type.

Atorvastatin↗

PubMed1970

Aspects of the stereochemistry of torularhodin biosynthesis.

1. The incorporation of [2-(14)C]acetate, [2-(14)C]mevalonic acid and [2-(14)C,2-(3)H(2)]-mevalonic acid into torulene and torularhodin by Rhodotorula rubra and Rhodotorula glutinis was studied. 2. A recovery of 14.3% of the label was obtained on decarboxylation of the torularhodin biosynthesized from [2-(14)C]mevalonic acid. 3. An analysis of the (3)H/(14)C ratio in torularhodin gave a value of 9.44:8. 4. These results, obtained by different experimental techniques, show that the reactions in the conversion of the dimethyl group of isopentenyl pyrophosphate into the 16',17'-position of torularhodin must be free from randomization. A mechanism for the isomerization of isopentenyl pyrophosphate to dimethylallyl pyrophosphate is suggested.

Acetates↗

PubMed1999

Effect of the hypocholesterolemic agent YM-16638 on cholesterol biosynthesis activity and apolipoprotein B secretion in HepG2 and monkey liver.

YM-16638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl]thio]-1,3,4-++ +thiadiazol-2-yl] thio] acetic acid) showed a strong hypocholesterolemic effect in humans and monkeys. To clarify the mechanism of this hypocholesterolemic effect, the action of YM-16638 on cholesterol biosynthesis in the cultured human hepatoma cell line HepG2 and cynomolgus monkey liver was examined. Cholesterol biosynthesis activity derived from [14C]acetic acid, [3H/14C]mevalonic acid or [14C]isopentenyl pyrophosphate substrates was significantly decreased, but not that from [3H]farnesyl pyrophosphate or [3H]squalene substrates in HepG2 cells treated with YM-16638. Simultaneously, treatment of these cells with YM-16638 changed neither the rate of apolipoprotein B synthesis from [35S]methionine nor its secretion. In addition, the activities of hepatic cholesterol biosynthesis enzymes HMG-CoA reductase, mevalonate kinase (MK), isopentenyl pyrophosphate isomerase (IPPI), farnesyl pyrophosphate synthase (FPPS), squalene synthase and squalene epoxidase were measured in monkeys fed a diet supplemented with YM-16638. Among these enzymes, MK, IPPI and FPPS activities in the YM-16638-treated group significantly decreased by 38%, 56% and 30%, respectively, when compared to those from control animals receiving no drug treatment. These results indicate that YM-16638 has the characteristics of a cholesterol biosynthesis inhibitor.

Alkyl and Aryl Transferases↗

PubMed2004

Solid phase extraction procedure for urinary organic acid analysis by gas chromatography mass spectrometry.

We have developed a solid phase extraction procedure for the detection of organic acids by GC-MS using a strong anion exchange column (Sep-Pak Vac RC, Accell Plus QMA cartridge). Extraction efficiencies of 25 organic acids were established by analyzing standards in water based solutions. High extraction efficiencies (90 to 100%) were found for many of the compounds studied. We estimated the limit of detection for 48 organic acids and glycine conjugates. They were below 5 nmole with the exception of malonic and oxalic acids and mevalonic acid lactone. This method provides the advantage of higher recoveries for a wide range of compounds of interest and therefore can be a potential alternative to liquid-liquid extraction for organic acid screening. It is especially sensitive for the detection of some polar compounds, such as 3-OH-glutaric and N-acetylaspartic acids.

Acids↗

PubMed1993

Production of an anti-allergic triterpene bryonolic acid, by plant cell cultures.

Cell suspension cultures of Luffa cylindrica, Citrullus lanatus, and related cucurbitaceous plants accumulate large quantities of bryonolic acid (3 beta-hydroxy-D:C-friedoolean-8-en-29-oic acid) [1], an acidic, pentacyclic triterpene found exclusively in the roots of the intact plants. This compound could readily be isolated from cultured cells with CHCl3 and purified simply by recrystallization. Pharmacological tests using mice demonstrated that bryonolic acid or its derivative is active against at least three types of allergies and that its activity could be increased significantly by preparing synthetic derivatives, in particular a potassium salt of its succinate ester. The biosynthesis of bryonolic acid from mevalonic acid via isomultiflorenol has been elucidated by tracer and enzymological experiments using cultured cells of watermelon both in vitro and in vivo. Furthermore, cell fractionation and electron microscopic studies on subcellular structures of luffa cells suggested that minute vesicles originating from elongated, rough endoplasmic reticulum probably play an important role in the transport of bryonolic acid which largely accumulates in the cell wall of cultured cells. The results obtained from the present study indicate that plant cell culture would be useful not only as a biological system for elucidating biosynthetic mechanisms but also as a potential source of new pharmacologically active compounds.

Animals↗

PubMed1970

Inhibitory Effect of Carbohydrate on Flowering in Lemna perpusilla: II. Reversal by Glycine and l-Aspartate. Correlation with Reduced Levels of beta-Carotene and Chlorophyll.

Flowering of Lemna perpusilla strain 6746 grown on 0.1 strength Hutner's medium in short days was inhibited by sucrose, glucose, fructose, and mannose, but not by various other sugars or metabolic intermediates. Only those sugars that inhibited flowering supported heterotrophic growth. Experiments with a single inductive long night indicated that an early stage in flowering was the sugar-sensitive process. Inhibition of flowering by carbohydrates was accompanied by reduced levels of chlorophyll and beta-carotene. The inhibitory effects of carbohydrates on flowering were partially reversed by iminodiacetate, glycine, and l-aspartate but not by d-aspartate, ethylenediaminetetraacetate, acetate, delta-aminolevulinic acid, or mevalonic acid. The possibility is discussed that carbohydrate repression of flowering and of chloroplast pigments resulted from inadequate levels of amino acids.

Journal Article↗

PubMed2000

Human serum paraoxonase (PON1) isozymes Q and R hydrolyze lactones and cyclic carbonate esters.

It is well established that human serum paraoxonase (PON1) catalyzes the hydrolysis of organophosphate insecticides and nerve agents, as well as that of a number of aromatic carboxylic acid esters. Our laboratory has recently found a new class of PON1 substrates that includes at least 30 lactones and cyclic carbonate esters. The lactone substrates vary in their ring size from 4 to 7 atoms. Substituents on the ring carbons may enhance or reduce the rate of lactone hydrolysis. An appreciable degree of stereospecificity exists with some activities differing up to 9-fold between enantiomers (i.e., S-alpha-hydroxy-gamma-butyrolactone is hydrolyzed 5 to 9 times faster than the R form). Thiolactones are hydrolyzed less efficiently, and some lactams are potent inhibitors. Four lactone-containing drugs-spironolactone, mevastatin, simvastatin, and lovastatin-have been identified as substrates for PON1. All lactone substrates are hydrolyzed by both the Q and R isozymes of human serum PON1. However, some lactone substrates are hydrolyzed faster by the Q than R isozyme, whereas others show a reverse preference. Moreover, these new substrates include homogentisic acid lactone, mevalonic acid lactone, homocysteine thiolactone, and gamma-hydroxybutyric acid lactone-all lactone forms of endogenous compounds. It is reasonable to expect that further investigations may uncover PON1 lactone substrates that are, themselves, endogenous compounds. In this article we characterize the basic enzymatic properties of PON1's newly identified hydrolytic activities with lactone and cyclic carbonate ester substrates and compare these properties with those of representative arylesters and organophosphates.

Aryldialkylphosphatase↗

PubMedDate not supplied

Antitumor effect of geranylamine derivatives on human hepatoma.

In this study, we examined the antitumor activities of isoprenoid derivatives conjugated with substrates of energy metabolism in human hepatoma-bearing athymic mice. Among these compounds, N-geranylpyruvic amide, N-geranyl-p-pyruvaminobenzoic amide, N,N'-digeranylmalic diamide and N,N'-digeranyl-O-acetylmalic diamide had strong antitumor effects. These geranylamine derivatives also inhibited in vitro cell growth. Sugar conjugates of geranylamine, geranic acid and mevalonic acid did not show any antitumor effect in vivo or in vitro. Although the geranylamine derivatives had no impact on the cell cycle distribution at 24 h, a sub-G1 (apoptotic) peak of varying magnitude was seen in DNA histograms of cells treated with the derivatives for 48 h. However, the geranylamine derivatives did not inhibit protein isoprenylation, which has been reported in cancer cells treated with several natural isoprenoids. These results suggest that the geranylamine derivatives conjugated with malic acid and pyruvic acid have a different mechanism of antitumor activity from that of natural isoprenoids.

Animals↗

PubMed1989

Contrasting effects of lovastatin and cholestyramine on low-density lipoprotein cholesterol and 24-hour urinary mevalonate excretion in patients with heterozygous familial hypercholesterolemia.

To further validate the usefulness of quantitative measurements of urinary mevalonic acid excretion as an indicator of rates of cholesterol biosynthesis, we have determined the 24-hour urinary excretion of mevalonic acid in patients with heterozygous familial hypercholesterolemia treated with drugs that have opposing effects on cholesterol biosynthesis. In patients with familial hypercholesterolemia treated with the bile acid sequestrant cholestyramine (16 gms/day), urinary mevalonate excretion increased by 28%, whereas low-density lipoprotein cholesterol concentrations decreased by 21%. In patients with familial hypercholesterolemia treated with the 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor lovastatin (80 mg/day), concentrations of low-density lipoprotein cholesterol and the urinary excretion of mevalonate both decreased (by 40% and 34%, respectively). When cholestyramine was used in combination with lovastatin, low-density lipoprotein cholesterol levels decreased by an additional 14% as compared to monotherapy with lovastatin; urinary mevalonate excretion rose by (25%), but the magnitude of this increase was not statistically significant. We conclude that rates of excretion of urinary mevalonic acid (which may reflect rates of whole body cholesterol biosynthesis) in patients with FH decrease on therapy with lovastatin and increase in response to cholestyramine treatment. When used in combination, these drugs counteract each other's effects on cholesterol synthesis, but low-density lipoprotein cholesterol concentrations decrease further. Measurement of urinary mevalonate excretion affords a practical means of assessing the comparable effects of different dietary or pharmaceutical manipulations on cholesterol biosynthesis in human beings.

Adult↗

PubMed2006

A role for geranylgeranylation in interleukin-1beta secretion.

OBJECTIVE: Mevalonate kinase deficiency (MKD) is an autosomal-recessive disorder characterized by recurring episodes of inflammation. MK catalyzes the phosphorylation of mevalonic acid, which is an early step in isoprenoid biosynthesis. The goal of our study was to determine whether a temporary shortage of certain isoprenoid end products and/or the accumulation of mevalonic acid is the cause of interleukin-1beta (IL-1beta) secretion in MKD. METHODS: We studied the effect of the addition of intermediate metabolites and inhibitors of the isoprenoid biosynthesis pathway on IL-1beta secretion by peripheral blood mononuclear cells (PBMCs) of patients with MKD and healthy controls. RESULTS: Inhibition of enzymes involved in geranylgeranyl pyrophosphate (GGPP) synthesis or geranylgeranylation of proteins led to a marked increase of lipopolysaccharide-stimulated IL-1beta secretion in PBMCs of control subjects. Furthermore, the increased IL-1beta secretion by PBMCs of patients with MKD was reversed by supplementation with GGPP as well as with mevalonic acid. IL-1beta secretion was increased only when control PBMCs were incubated with excessive amounts of mevalonic acid. Finally, a reduction in IL-1beta secretion by MKD PBMCs was also observed when sterol biosynthesis was inhibited, favoring nonsterol isoprenoid biosynthesis. CONCLUSION: Our results indicate that a shortage of geranylgeranylated proteins, rather than an excess of mevalonate, is likely to cause increased IL-1beta secretion by PBMCs of patients with MKD.

Anti-Inflammatory Agents↗

PubMed1996

The effects of pravastatin, an HMG-CoA reductase inhibitor, on cell viability and DNA production of rat hepatocytes.

Some metabolites and products of mevalonic acid are involved in various cellular functions, particularly cell growth. In this study, we assessed the effects of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on cell viability and DNA production of rat hepatocytes stimulated with epidermal growth factor. Pravastatin (0.1 to 10 microM) induced a dose-dependent reduction of DNA synthesis, assessed by 3H-thymidine incorporation in rat hepatocytes, which dropped by approximately 60% at a drug concentration of 10 microM. This suppression of DNA synthesis was nearly reversed by exogenous mevalonic acid, but was not prevented by purified low-density lipoprotein cholesterol. Pravastatin did not affect the mitochondrial reduction of Dimethylthiazolyl-diphenyl-tetrazolium bromide (MTT), but induced apoptotic change as assessed by nuclear chromatin staining. This apoptotic change was also reversed by exogenous mevalonic acid. These results indicate that mevalonic acid metabolites are necessary for DNA synthesis by rat hepatocytes stimulated by epidermal growth factor and for suppressing cell death.

Adenine↗

PubMed1997

Feasibility of an immunoassay for mevalonolactone.

Mevalonic acid is a key intermediate in a broad spectrum of cellular biological processes and their regulation. Availability of a rapid, sensitive and accurate method for its assay would be highly useful. Therefore, the feasibility of developing an immunoassay for mevalonic acid in biological samples was explored. The strategy employed was to synthesize several racemic haptens structurally resembling R-mevalonolactone, the cyclic form of mevalonic acid present at lower pH and presumed to be more antigenic. Two of these haptens were coupled to keyhole limpet hemocyanin, and the resulting conjugates were used successfully to generate antibodies in rabbits. The first antiserum bound to R,S-mevalonolactone much more effectively at pH 4.0 than at pH 6.0, consistent with the structural resemblance of the haptens to the lactone form. This antiserum also bound the free hapten from which it was generated and two others of different structure with comparable effectiveness; and slightly better than it bound R,S-mevalonolactone at pH 4.0. Similar results were obtained with the antiserum to the second hapten. The binding of either antiserum to the natural enantiomer, R-mevalonolactone, was 20 times weaker than to R,S-mevalonolactone, suggesting that the nonbiological enantiomer was more antigenic. Nevertheless, the results demonstrate that an immunochemical approach to accurate quantitation of mevalonic acid in biological samples is feasible.

Animals↗

PubMed1994

Presqualene metabolism in two species of Lagenidium.

The fate of precursors of the isoprenoid pathway was studied in the sterol auxotroph Lagenidium giganteum and in the positive control organism Lagenidium callinectes. Acetate derived from glucose and mevalonic acid was converted to sterols and fatty acids in L. callinectes. Lagenidium giganteum converted mevalonic acid to sterols and fatty acids, but glucose-derived acetate was not utilized for sterol synthesis. The results showed that the defect in the isoprenoid pathway of L. giganteum occurs at the level of the beta-hydroxy-beta-methylglutarylcoenzyme A reductase-synthase complex. Various aspects of this defect are discussed relative to metabolism of the organism.

Acetates↗

PubMed1997

In vitro and in vivo antiproliferative effects of simvastatin, an HMG-CoA reductase inhibitor, on human glioma cells.

We analyzed the antiproliferative effect of simvastatin (SV), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on human glioma cell lines. Inhibition of cell growth with SV was observed in all cell lines tested. Different culture conditions altered this inhibition of growth: the lower the concentration of fetal bovine serum (FBS) in the medium, the higher the inhibitory effect of SV on glioma cells. On morphological examination, we found that most of the cells exposed to SV became rounded and the proportion of floating cells was increased in a time-dependent manner. Then we examined whether exogenously added mevalonic acid reversed the growth inhibitory effect of SV. Exogenous mevalonic acid suppressed the inhibitory effect of SV on glioma cells in a dose-dependent manner. SV also enhanced the expression of low-density lipoprotein (LDL) receptor on glioma cells. We also found that peroxidized LDL (p-LDL) was cytotoxic to glioma cells and that SV had additive effects on pLDL-induced cytotoxicity. In a mouse model, growth of glioma cells inoculated into nude mice was inhibited by intratumoral injection of both SV and peroxidized LDL. These results indicate that mevalonic acid or a metabolite in the cholesterol synthesis pathway is necessary for the growth of glioma cells and that simvastatin and/or peroxidized LDL should be examined further as potential therapeutic agents for gliomas.

Animals↗