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Cell Transplantation 2022Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for... (Review)
Review
Although brain tumors occur less frequently than other forms of cancer, they have one of the bleakest prognoses with low survival rates. The conventional treatment for brain tumors includes surgery, radiotherapy, and chemotherapy. However, resistance to treatment remains a problem with recurrence shortly following. The resistance to treatment may be caused by cancer stem cells (CSCs), a subset of brain tumor cells with the affinity for self-renewal and differentiation into multiple cell lineages. An emerging approach to targeting CSCs in brain tumors is through repurposing the lipid-lowering medication, lovastatin. Lovastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor that impacts the mevalonate pathway. The inhibition of intermediates in the mevalonate pathway affects signaling cascades and oncogenes associated with brain tumor stem cells (BTSC). In this review, we show the possible mechanisms where lovastatin can target BTSC for different varieties of malignant brain tumors.
Topics: Brain; Brain Neoplasms; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Mevalonic Acid
PubMed: 35670207
DOI: 10.1177/09636897221102903 -
Drug Intelligence & Clinical Pharmacy 1988Lovastatin is the first 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of primary hypercholesterolemia. It is indicated... (Review)
Review
Lovastatin is the first 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor approved for the treatment of primary hypercholesterolemia. It is indicated as adjunctive therapy to dietary control and should be initiated at 20 mg/d in the evening. With higher dosages, twice-daily dosing is preferred, particularly when the dosage reaches the maximum recommended 80 mg/d. Compared with other drugs available, lovastatin has been shown to have good efficacy and a low incidence of side effects. Limited pharmacokinetic information available from the manufacturer reports absorption approximately 30 percent, protein binding greater than 95 percent, and a dual pathway for elimination through both urine (10 percent) and feces (83 percent). The drug has been clinically tested versus placebo and in combination with other cholesterol-lowering drugs. Lovastatin is effective in lowering total cholesterol and low-density lipoprotein cholesterol by 25-30 percent, with nonfamilial (hypercholesterolemic) patients responding better than those with the familial form of the disease. One percent of lovastatin patients have discontinued therapy because of intolerable side effects. The most common complaints are flatulence and diarrhea; more severe abnormalities include elevation of liver enzymes and an unclear propensity for producing lens opacities. The monthly cost to a patient taking 20 mg/d is approximately $44. Although the drug should be added to hospital formularies, long-term safety experience and competition from other HMG-CoA reductase inhibitors will determine lovastatin's final therapeutic role.
Topics: Humans; Hypercholesterolemia; Lovastatin
PubMed: 3046888
DOI: 10.1177/106002808802200703 -
Biotechnology Advances Nov 2015Lovastatin, composed of secondary metabolites produced by filamentous fungi, is the most frequently used drug for hypercholesterolemia treatment due to the fact that... (Review)
Review
Lovastatin, composed of secondary metabolites produced by filamentous fungi, is the most frequently used drug for hypercholesterolemia treatment due to the fact that lovastatin is a competitive inhibitor of HMG-CoA reductase. Moreover, recent studies have shown several important applications for lovastatin including antimicrobial agents and treatments for cancers and bone diseases. Studies regarding the lovastatin biosynthetic pathway have also demonstrated that lovastatin is synthesized from two-chain reactions using acetate and malonyl-CoA as a substrate. It is also known that there are two key enzymes involved in the biosynthetic pathway called polyketide synthases (PKS). Those are characterized as multifunctional enzymes and are encoded by specific genes organized in clusters on the fungal genome. Since it is a secondary metabolite, cultivation process optimization for lovastatin biosynthesis has included nitrogen limitation and non-fermentable carbon sources such as lactose and glycerol. Additionally, the influences of temperature, pH, agitation/aeration, and particle and inoculum size on lovastatin production have been also described. Although many reviews have been published covering different aspects of lovastatin production, this review brings, for the first time, complete information about the genetic basis for lovastatin production, detection and quantification, strain screening and cultivation process optimization. Moreover, this review covers all the information available from patent databases covering each protected aspect during lovastatin bio-production.
Topics: Aspergillus; Fermentation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lovastatin; Metabolic Engineering
PubMed: 25868803
DOI: 10.1016/j.biotechadv.2015.04.001 -
Cellular Signalling Nov 2021Lovastatin, a secondary metabolite isolated from fungi, is often used as a representative drug to reduce blood lipid concentration and treat hypercholesterolemia. Its... (Review)
Review
Lovastatin, a secondary metabolite isolated from fungi, is often used as a representative drug to reduce blood lipid concentration and treat hypercholesterolemia. Its structure is similar to that of HMG-CoA. Lovastatin inhibits the binding of the substrate to HMG-CoA reductase, and strongly competes with HMG-CoA reductase (HMGR), thereby exerting a hypolipidemic effect. Further, its safety has been confirmed in vivo and in vitro. Lovastatin also has anti-inflammatory, anti-cancer, and neuroprotective effects. Therefore, the biological activity of lovastatin, especially its anti-cancer effect, has garnered research attention. Several in vitro studies have confirmed that lovastatin has a significant inhibitory effect on cancer cell viability in a variety of cancers (such as breast, liver, cervical, lung, and colon cancer). At the same time, lovastatin can also increase the sensitivity of some types of cancer cells to chemotherapeutic drugs and strengthen their therapeutic effect. Lovastatin inhibits cell proliferation and regulates cancer cell signaling pathways, thereby inducing apoptosis and cell cycle arrest. This article reviews the structure, biosynthetic pathways, and applications of lovastatin, focusing on the anti-cancer effects and mechanisms of action.
Topics: Apoptosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Lovastatin; Neoplasms
PubMed: 34438015
DOI: 10.1016/j.cellsig.2021.110122 -
Food & Function Jul 2020Lovastatin/monacolin K (MK) is used as a lipid lowering drug, due to its effective hypercholesterolemic properties, comparable to synthetic statins. Lovastatin's... (Review)
Review
Lovastatin/monacolin K (MK) is used as a lipid lowering drug, due to its effective hypercholesterolemic properties, comparable to synthetic statins. Lovastatin's biosynthetic pathway and gene cluster composition have been studied in depth in Aspergillus terreus. Evidence shows that the MK biosynthetic pathway and gene cluster in Monascus sp. are similar to those of lovastatin in A. terreus. Currently, research efforts have been focusing on the metabolic regulation of MK/lovastatin synthesis, and the evidence shows that a combination of extracellular and intracellular factors is essential for proper MK/lovastatin metabolism. Here, we comprehensively review the research progress on MK/lovastatin biosynthetic pathways, its synthetic precursors and inducing substances and metabolic regulation, with a view to providing reference for future research on fungal metabolism regulation and metabolic engineering for MK/lovastatin production.
Topics: Acetyl-CoA Carboxylase; Aspergillus; Fungal Proteins; Gene Expression Regulation, Fungal; Lovastatin; Monascus; Promoter Regions, Genetic
PubMed: 32555902
DOI: 10.1039/d0fo00691b -
Clinical Pharmacy Jan 1988The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of lovastatin are reviewed. Lovastatin is the first... (Review)
Review
The chemistry, pharmacology, pharmacokinetics, clinical efficacy, dosage and administration, and adverse effects of lovastatin are reviewed. Lovastatin is the first agent marketed in a new class of pharmacologic compounds called the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors. By competitively inhibiting HMG CoA reductase, the drug disrupts the biosynthesis of cholesterol in hepatic and peripheral cells. This increases the synthesis of low-density-lipoprotein (LDL) receptors and thereby increases the uptake of LDL cholesterol from the plasma. In doses of 20 to 80 mg daily, lovastatin decreases total and LDL cholesterol concentrations 25 to 45%. It also substantially reduces concentrations of triglycerides, very-low-density-lipoprotein (VLDL) cholesterol, and apolipoprotein B and slightly increases high-density-lipoprotein (HDL) cholesterol concentrations. Lovastatin is effective in patients with heterozygous familial and nonfamilial (polygenic) hypercholesterolemia but is ineffective in patients with homozygous familial hypercholesterolemia. It is also effective in combination with bile acid sequestrants, nicotinic acid, and gemfibrozil. Administration of lovastatin once daily in the evening (to enhance compliance) or twice daily is recommended to maximize the drug's cholesterol-lowering effects. Headache and gastrointestinal complaints are the most common adverse effects. Treatment has been withdrawn from 1.9% of patients receiving the drug because of elevated aminotransferase concentrations. The relationship of lovastatin to the development of lens opacities requires further evaluation. Lovastatin is highly effective in the treatment of primary hypercholesterolemia and represents an important therapeutic advance. Safety with long-term use and effect on coronary heart disease remain to be established.
Topics: Humans; Lovastatin
PubMed: 3278832
DOI: No ID Found -
Pharmacotherapy 1987Lovastatin is a potent new drug for lowering serum cholesterol through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme for... (Review)
Review
Lovastatin is a potent new drug for lowering serum cholesterol through inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. Metabolic studies with lovastatin in healthy volunteers and patients with hypercholesterolemia suggest reduced synthesis of low-density lipoprotein cholesterol (LDL-C) as well as enhanced catabolism LDL-C mediated through LDL receptors as the principal mechanisms for lipid-lowering effects. Total cholesterol and LDL-C are reduced by 30% or more on average when added to baseline therapy, with the effects being more pronounced in nonfamilial than in familial hypercholesterolemia. Optimal dosing appears to be 20 mg given twice a day. The most common adverse effects are gastrointestinal, while the most serious are elevated transaminase levels and the potential for lens opacities. Lovastatin is the first of a new class of lipid-lowering agents, and is effective when added to diet therapy or in combination with other drugs.
Topics: Cholesterol; Humans; Lovastatin
PubMed: 3328165
DOI: 10.1002/j.1875-9114.1987.tb03524.x -
Drugs 2003Lovastatin extended release (ER) provides a new form of delivery for lovastatin, an HMG-CoA reductase inhibitor. Lovastatin ER delivers the drug in a more sustained... (Review)
Review
UNLABELLED
Lovastatin extended release (ER) provides a new form of delivery for lovastatin, an HMG-CoA reductase inhibitor. Lovastatin ER delivers the drug in a more sustained fashion, as shown by a smoother plasma concentration-time profile, a lower maximum plasma concentration and a prolonged half-life compared with that of lovastatin immediate release (IR). At dosages of 10-60 mg/day, lovastatin ER significantly reduced levels of total cholesterol, low density lipoprotein (LDL)-cholesterol and triglycerides, and increased levels of high density lipoprotein-cholesterol, in patients with primary hypercholesterolaemia in a randomised, double-blind study of 12 weeks' duration. These effects were maintained in a 6-month extension study in which patients received lovastatin 40 or 60 mg/day. In a randomised 4-week study in 24 patients with primary hypercholesterolaemia, the reduction in plasma LDL-cholesterol levels was significantly greater with lovastatin ER 40 mg/day than with the IR formulation administered at the same dosage. Lovastatin ER was well tolerated in all studies and adverse events were usually mild to moderate and transient. The tolerability profile of lovastatin ER was similar to that of lovastatin IR. There were no reports of clinically relevant elevations in liver transaminases or creatine phosphokinase attributed to the drug in recipients of lovastatin ER.
CONCLUSION
The ER formulation of lovastatin provides smooth and sustained delivery of this established and well-tolerated agent over the dosage interval, significantly reducing LDL-cholesterol in patients with primary hypercholesterolaemia. If, as expected, the beneficial changes in lipid levels are maintained during long-term treatment and further clinical experience confirms the greater efficacy of the lovastatin ER formulation than the IR formulation, then lovastatin ER is likely to supplant lovastatin IR and provide a useful option in the management of patients with dyslipidaemia and prevention of coronary heart disease.
Topics: Absorption; Administration, Oral; Anticholesteremic Agents; Coronary Disease; Delayed-Action Preparations; Dose-Response Relationship, Drug; Humans; Hypercholesterolemia; Lovastatin
PubMed: 12656649
DOI: 10.2165/00003495-200363070-00007 -
Food and Chemical Toxicology : An... Sep 2019Monacolin K (MK) is the principal active substance in Monascus-fermentation products (e.g. red yeast rice). MK is effective in reducing cholesterol levels in humans and... (Review)
Review
Monacolin K (MK) is the principal active substance in Monascus-fermentation products (e.g. red yeast rice). MK is effective in reducing cholesterol levels in humans and has been widely used as a lipid-lowering drug. The mechanism for this is through a high degree of competitive inhibition of the rate-limiting enzyme HMG-CoA reductase (HMGR) in the cholesterol synthesis pathway. In addition to lowering blood lipid levels, MK also prevents colon cancer, acute myeloid leukemia and neurological disorders such as Parkinson's disease and type I neurofibromatosis. The aim of this manuscript is to comprehensively review the progress in the study of the biological activity of MK and its imechanism of action in reducing blood lipid concentration, prevention of cancer and its neuroprotective, anti-inflammatory and antibacterial properties. This review provides a reference for future applications of MK in functional foods and medicine.
Topics: Animals; Biological Products; Functional Food; Humans; Lovastatin
PubMed: 31207306
DOI: 10.1016/j.fct.2019.110585 -
Drugs Oct 1988Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and... (Review)
Review
Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and apolipoprotein B concentrations, and increases LDL receptor activity without adverse effects on other products in the cholesterol pathway. In patients with heterozygous familial or polygenic (non-familial) hypercholesterolaemia, oral lovastatin 20 to 40 mg twice daily reduces plasma total cholesterol and LDL-cholesterol concentrations by 25 to 40% over a period of several weeks. Lovastatin also produces decreases in plasma triglyceride and VLDL-cholesterol concentrations, although to a lesser extent. In addition, small though significant increases in HDL-cholesterol concentrations have been observed. Combined administration of lovastatin with other lipid-lowering drugs results in further reductions in plasma total and LDL-cholesterol concentrations beyond those seen with either drug alone. From findings in short term studies, lovastatin appears to be well tolerated with a low incidence of side effects. However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established. As would be expected at this relatively early stage of its clinical 'life,' lovastatin has not yet been studied in a manner that would determine its effect on cardiovascular mortality during long term administration. Nevertheless, if the substantial improvements to patients' lipid and lipoprotein profiles observed in short term studies are maintained during long term administration, then lovastatin will have an important role in the pharmacological management of hyperlipidaemia.
Topics: Humans; Hyperlipidemias; Lovastatin
PubMed: 3069436
DOI: 10.2165/00003495-198836040-00003