Simvastatin and Its Role in Anti-Inflammation and Cancer Therapy: A Review
DOI:
https://doi.org/10.21276/a6gmys54Keywords:
Statins, Simvastatin, CVD, Inflammation, CancerAbstract
3-Hydroxy-3-methylglutaryl-coenzyme, a reductase inhibitors (statins) are widely used drugs to reduce lipid levels by inhibiting cholesterol biosynthesis. Simvastatin, a lipophilic statin is one of the most frequently prescribed statin drugs throughout the world due to profound reductions in LDL-C with excellent tolerability, with very little risk of important adverse effects, to a lower extent. It also reduce triglycerides and increase high-density lipoprotein cholesterol levels. Beside this, studies on simvastatin have shown to exhibit numerous pleiotropic effects, has beneficial effect on endothelial function, smooth muscle cell function, haemostasis, vascular wall function, LDL oxidation, kidney diseases, inflammation and anticarcinogenic effects on many types of cancer including prostate, breast hepatic and colon carcinoma. In this review, we present an overview of simvastatin and its relevance in anti-inflammation and cancer management.
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References
Bays H. Statin safety: an overview and assessment of the data--2005. Am J
Cardiol. 2006;97(8A):6C-26C. doi:10.1016/j.amjcard.2005.12.006
Kolovou G. The treatment of coronary heart disease: an update. Part 3: Statins
beyond cholesterol lowering. Curr Med Res Opin. 2001;17(1):34-37.
Ramkumar S, Raghunath A, Raghunath S. Statin Therapy: Review of Safety
and Potential Side Effects. Acta Cardiol Sin. 2016;32(6):631-639.
doi:10.6515/acs20160611a
Longo J, van Leeuwen JE, Elbaz M, Branchard E, Penn LZ. Statins as
Anticancer Agents in the Era of Precision Medicine. Clin Cancer Res.
;26(22):5791-5800. doi:10.1158/1078-0432.CCR-20-1967
Duarte JA, de Barros ALB, Leite EA. The potential use of simvastatin for
cancer treatment: A review. Biomed Pharmacother. 2021;141:111858.
doi:10.1016/j.biopha.2021.111858
Hadjiphilippou S, Ray KK. Cholesterol-Lowering Agents. Circ Res.
;124(3):354-363. doi:10.1161/CIRCRESAHA.118.313245
Vahedian-Azimi A, Bianconi V, Makvandi S, et al. A systematic review and
meta-analysis on the effects of statins on pregnancy
outcomes. Atherosclerosis. 2021;336:1-11.
doi:10.1016/j.atherosclerosis.2021.09.010
Grodos D, Tonglet R. Scandinavian simvastatin study (4S). Lancet.
;344(8939-8940):1768.
Simões RG, Bernardes CE, Diogo HP, Agapito F, Minas da Piedade ME.
Energetics and structure of simvastatin. Mol Pharm. 2013;10(7):2713-2722.
doi:10.1021/mp400132r
National Center for Biotechnology Information. PubChem Compound
Summary for CID 54454,
Simvastatin. https://pubchem.ncbi.nlm.nih.gov/compound/Simvastatin.
Hoffman WF, Alberts AW, Anderson PS, Chen JS, Smith RL, Willard AK. 3-
Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 4. Side chain ester
derivatives of mevinolin. J Med Chem. 1986 May;29(5):849-52. doi:
1021/jm00155a040. PMID: 3634830.
Robinson JG. Simvastatin: present and future perspectives. Expert Opin
Pharmacother. 2007;8(13):. doi:10.1517/14656566.8.13.2159
Vickers S, Duncan CA, Chen IW, Rosegay A, Duggan DE. Metabolic
disposition studies on simvastatin, a cholesterol-lowering prodrug. Drug Metab
Dispos. 1990;18(2):138-145.
Prueksaritanont T, Subramanian R, Fang X, et al. Glucuronidation of statins in
animals and humans: a novel mechanism of statin lactonization. Drug Metab
Dispos. 2002;30(5):505-512. doi:10.1124/dmd.30.5.505
Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular
Society Guidelines for the Management of Dyslipidemia for the Prevention of
Cardiovascular Disease in the Adult. Can J Cardiol. 2016;32(11):1263-1282.
doi:10.1016/j.cjca.2016.07.510
Patel, R.; Patel, M. Preparation, characterization, and dissolution behavior of a
solid dispersion of Simvastatin with polyethylene glycol 4000 and
polyvinylpyrrolidone K30. J. Dispersion Sci. Technol. 2008, 29, 193−204.
Silva, T. D.; Arantes, V. T.; Resende, J. A. L. C.; Speziali, N. L.; de Oliveira, R.
B.; Vianna-Soares, C. D. Preparation and character- ization of solid dispersion
of simvastatin. Drug Dev. Ind. Pharm. 2010, 36, 1348−1355
FDA Label - Simvastatin [File]
Health Canada Monograph - Simvastatin [File]
Grundy SM, Stone NJ. 2018 American Heart Association/American College of
Cardiology Multisociety Guideline on the Management of Blood Cholesterol:
Primary Prevention. JAMA Cardiol. 2019 May 1;4(5):488-489. doi:
1001/jamacardio.2019.0777. PMID: 30969322.
Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study
Group. Prevention of cardiovascular events and death with pravastatin in
patients with coronary heart disease and a broad range of initial cholesterol
levels. N Engl J Med. 1998;339(19):1349-1357.
doi:10.1056/NEJM199811053391902
Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid
lowering with statins after acute coronary syndromes [published correction
appears in N Engl J Med. 2006 Feb 16;354(7):778]. N Engl J Med.
;350(15):1495-1504. doi:10.1056/NEJMoa040583
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive protein. N Engl J Med.
;359(21):2195-2207. doi:10.1056/NEJMoa0807646
Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P,
Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE. Effect of two intensive
statin regimens on progression of coronary disease. N Engl J Med. 2011 Dec
;365(22):2078-87. doi: 10.1056/NEJMoa1110874. Epub 2011 Nov 15. PMID:
Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study
of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a
randomised placebo-controlled trial. Lancet. 2002;360(9326):7-22.
doi:10.1016/S0140-6736(02)09327-3
Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson
J, et al. The effects of lowering LDL cholesterol with statin therapy in people at
low risk of vascular disease: meta-analysis of individual data from 27
randomised trials. Lancet. 2012;380(9841):581-590. doi:10.1016/S0140-
(12)60367-5
Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of
cardiovascular disease. Cochrane Database Syst Rev.
;2013(1):CD004816. Published 2013 Jan 31.
doi:10.1002/14651858.CD004816.pub5
Moghadasian MH. Clinical pharmacology of 3-hydroxy-3-methylglutaryl
coenzyme A reductase inhibitors. Life Sci. 1999;65(13):1329-1337.
doi:10.1016/s0024-3205(99)00199-x
Liao JK, Laufs U. Pleiotropic effects of statins. Annu Rev Pharmacol Toxicol.
;45:89-118. doi:10.1146/annurev.pharmtox.45.120403.095748
Weitz-Schmidt G, Welzenbach K, Brinkmann V, et al. Statins selectively inhibit
leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat
Med. 2001;7(6):687-692. doi:10.1038/89058
Carbonell T, Freire E. Binding thermodynamics of statins to HMG-CoA
reductase. Biochemistry. 2005;44(35):11741-11748. doi:10.1021/bi050905v
Cenedella RJ, Kuszak JR, Al-Ghoul KJ, Qin S, Sexton PS. Discordant
expression of the sterol pathway in lens underlies simvastatin-induced
cataracts in Chbb: Thom rats. J Lipid Res. 2003;44(1):198-211.
doi:10.1194/jlr.m200002-jlr200
Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC. Statins increase p21
through inhibition of histone deacetylase activity and release of promoterassociated HDAC1/2. Cancer Res. 2008;68(7):2375-2383. doi:10.1158/0008-
CAN-07-5807
Katano H, Pesnicak L, Cohen JI. Simvastatin induces apoptosis of EpsteinBarr virus (EBV)-transformed lymphoblastoid cell lines and delays
development of EBV lymphomas. Proc Natl Acad Sci U S A.
;101(14):4960-4965. doi:10.1073/pnas.0305149101
Weitz-Schmidt G, Welzenbach K, Brinkmann V, et al. Statins selectively inhibit
leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat
Med. 2001;7(6):687-692. doi:10.1038/89058
Zhou Q, Ruan ZR, Jiang B, Yuan H, Zeng S. Simvastatin pharmacokinetics in
healthy Chinese subjects and its relations with CYP2C9, CYP3A5, ABCB1,
ABCG2 and SLCO1B1 polymorphisms. Pharmazie. 2013;68(2):124-128.
Prueksaritanont T, Gorham LM, Ma B, et al. In vitro metabolism of simvastatin
in humans [SBT]identification of metabolizing enzymes and effect of the drug
on hepatic P450s. Drug Metab Dispos. 1997;25(10):1191-1199.
Prueksaritanont T, Ma B, Yu N. The human hepatic metabolism of simvastatin
hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br J Clin
Pharmacol. 2003;56(1):120-124. doi:10.1046/j.1365-2125.2003.01833.x
Keskitalo JE, Zolk O, Fromm MF, Kurkinen KJ, Neuvonen PJ, Niemi M.
ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin
and rosuvastatin. Clin Pharmacol Ther. 2009;86(2):197-203.
doi:10.1038/clpt.2009.79
Pasanen MK, Neuvonen M, Neuvonen PJ, Niemi M. SLCO1B1 polymorphism
markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet
Genomics. 2006;16(12):873-879. doi:10.1097/01.fpc.0000230416.82349.90
SEARCH Collaborative Group, Link E, Parish S, et al. SLCO1B1 variants and
statin-induced myopathy--a genomewide study. N Engl J Med.
;359(8):789-799. doi:10.1056/NEJMoa0801936
Elsby R, Hilgendorf C, Fenner K. Understanding the critical disposition
pathways of statins to assess drug-drug interaction risk during drug
development: it's not just about OATP1B1. Clin Pharmacol Ther.
;92(5):584-598. doi:10.1038/clpt.2012.163
Tubic-Grozdanis M, Hilfinger JM, Amidon GL, et al. Pharmacokinetics of the
CYP 3A substrate simvastatin following administration of delayed versus
immediate release oral dosage forms. Pharm Res. 2008;25(7):1591-1600.
doi:10.1007/s11095-007-9519-6
Prueksaritanont T, Gorham LM, Ma B, et al. In vitro metabolism of simvastatin
in humans [SBT]identification of metabolizing enzymes and effect of the drug
on hepatic P450s. Drug Metab Dispos. 1997;25(10):1191-1199.
Pedersen TR, Tobert JA. Simvastatin: a review. Expert Opin Pharmacother.
;5(12):2583-2596. doi:10.1517/14656566.5.12.2583
Kolodziejczyk AM, Targosz-Korecka M, Szymonski M. Nanomechanical testing
of drug activities at the cellular level: Case study for endothelium-targeted
drugs. Pharmacol Rep. 2017;69(6):1165-1172.
doi:10.1016/j.pharep.2017.06.007
Saggini A, Anogeianaki A, Maccauro G, et al. Cholesterol, cytokines and
diseases. Int J Immunopathol Pharmacol. 2011;24(3):567-581.
doi:10.1177/039463201102400303
Barale C, Frascaroli C, Senkeev R, Cavalot F, Russo I. Simvastatin Effects on
Inflammation and Platelet Activation Markers in Hypercholesterolemia. Biomed
Res Int. 2018;2018:6508709. Published 2018 Oct 1.
doi:10.1155/2018/6508709
Sparrow CP, Burton CA, Hernandez M, et al. Simvastatin has antiinflammatory and antiatherosclerotic activities independent of plasma
cholesterol lowering. Arterioscler Thromb Vasc Biol. 2001;21(1):115-121.
doi:10.1161/01.atv.21.1.115
Liu L, Moesner P, Kovach NL, et al. Integrin-dependent leukocyte adhesion
involves geranylgeranylated protein(s). J Biol Chem. 1999;274(47):33334-
doi:10.1074/jbc.274.47.33334
Weber C, Erl W, Weber KS, Weber PC. HMG-CoA reductase inhibitors
decrease CD11b expression and CD11b-dependent adhesion of monocytes to
endothelium and reduce increased adhesiveness of monocytes isolated from
patients with hypercholesterolemia. J Am Coll Cardiol. 1997;30(5):1212-1217.
doi:10.1016/s0735-1097(97)00324-0
Stanislaus R, Pahan K, Singh AK, Singh I. Amelioration of experimental
allergic encephalomyelitis in Lewis rats by lovastatin. Neurosci Lett.
;269(2):71-74. doi:10.1016/s0304-3940(99)00414-0
Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA
reductase inhibitor, on the expression of adhesion molecules on human
monocyte cell line. Int J Immunopharmacol. 1996;18(11):669-675.
doi:10.1016/s0192-0561(96)00068-9
Ikeda U, Shimada K: Statins and monocytes [letter]. Lancet 1999; 353:2070.
Rosenson RS, Tangney CC, Casey LC. Inhibition of proinflammatory cytokine
production by pravastatin. Lancet. 1999;353(9157):983-984.
doi:10.1016/S0140-6736(98)05917-0
Ferro D, Parrotto S, Basili S, Alessandri C, Violi F. Simvastatin inhibits the
monocyte expression of proinflammatory cytokines in patients with
hypercholesterolemia. J Am Coll Cardiol. 2000;36(2):427-431.
doi:10.1016/s0735-1097(00)00771-3
Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of
interleukin-6 and the risk of future myocardial infarction among apparently
healthy men. Circulation. 2000;101(15):1767-1772.
doi:10.1161/01.cir.101.15.1767
Ridker PM, Hennekens CH, Roitman-Johnson B, Stampfer MJ, Allen J.
Plasma concentration of soluble intercellular adhesion molecule 1 and risks of
future myocardial infarction in apparently healthy men. Lancet.
;351(9096):88-92. doi:10.1016/S0140-6736(97)09032-6
Blake GJ, Ridker PM. Are statins anti-inflammatory?. Curr Control Trials
Cardiovasc Med. 2000;1(3):161-165. doi:10.1186/cvm-1-3-161
Cubbon R, Kahn M, Kearney MT. Secondary prevention of cardiovascular
disease in type 2 diabetes and prediabetes: a cardiologist's perspective. Int J
Clin Pract. 2008;62(2):287-299. doi:10.1111/j.1742-1241.2007.01646.x
Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular
events in men and women with elevated C-reactive protein. N Engl J Med.
;359(21):2195-2207. doi:10.1056/NEJMoa0807646
Hu Y, Tong G, Xu W, et al. Anti-inflammatory effects of simvastatin on
adipokines in type 2 diabetic patients with carotid atherosclerosis. Diab Vasc
Dis Res. 2009;6(4):262-268. doi:10.1177/1479164109339966
Kanda H, Hamasaki K, Kubo K, et al. Antiinflammatory effect of simvastatin in
patients with rheumatoid arthritis. J Rheumatol. 2002;29(9):2024-2026.
Takeda N, Kondo M, Ito S, Ito Y, Shimokata K, Kume H. Role of RhoA
inactivation in reduced cell proliferation of human airway smooth muscle by
simvastatin. Am J Respir Cell Mol Biol. 2006;35(6):722-729.
doi:10.1165/rcmb.2006-0034OC
Shammas NW, Kapalis MJ, Deckert J, et al. Effectiveness of statin-gemfibrozil
combination therapy in patients with mixed hyperlipidemia: experience of a
community lipid clinic and safety review from the literature. Prev Cardiol.
;6(4):189-194. doi:10.1111/j.1520-037x.2003.02200.x
Mohrschladt MF, de Maat MP, Westendorp RG, Smelt AH. C-reactive protein
in patients with familial hypercholesterolemia: no effect of simvastatin
therapy. Atherosclerosis. 2001;157(2):491-494. doi:10.1016/s0021-
(00)00754-1
Lahera V, Goicoechea M, de Vinuesa SG, et al. Endothelial dysfunction,
oxidative stress and inflammation in atherosclerosis: beneficial effects of
statins. Curr Med Chem. 2007;14(2):243-248.
doi:10.2174/092986707779313381
Dichtl W, Dulak J, Frick M, et al. HMG-CoA reductase inhibitors regulate
inflammatory transcription factors in human endothelial and vascular smooth
muscle cells. Arterioscler Thromb Vasc Biol. 2003;23(1):58-63.
doi:10.1161/01.atv.0000043456.48735.20
Ortego M, Gómez-Hernández A, Vidal C, et al. HMG-CoA reductase inhibitors
reduce I kappa B kinase activity induced by oxidative stress in monocytes and
vascular smooth muscle cells. J Cardiovasc Pharmacol. 2005;45(5):468-475.
doi:10.1097/01.fjc.0000159042.50488.e5
Kolovou GD, Katerina A, Ioannis V, Cokkinos DV. Simvastatin: two decades in
a circle. Cardiovasc Ther. 2008;26(2):166-178. doi:10.1111/j.1527-
2008.00047.x
Tuomisto TT, Lumivuori H, Kansanen E, et al. Simvastatin has an antiinflammatory effect on macrophages via upregulation of an atheroprotective
transcription factor, Kruppel-like factor 2. Cardiovasc Res. 2008;78(1):175-184.
doi:10.1093/cvr/cvn007
Parmar KM, Nambudiri V, Dai G, Larman HB, Gimbrone MA Jr, GarciaCardena G. Statins exert endothelial atheroprotective effects via the KLF2
transcription factor. J Biol Chem 2005;280:26714–26719.
Lin Z, Kumar A, SenBanerjee S, et al. Kruppel-like factor 2 (KLF2) regulates
endothelial thrombotic function. Circ Res. 2005;96(5):e48-e57.
doi:10.1161/01.RES.0000159707.05637.a1
SenBanerjee S, Lin Z, Atkins GB, et al. KLF2 Is a novel transcriptional
regulator of endothelial proinflammatory activation. J Exp Med.
;199(10):1305-1315. doi:10.1084/jem.20031132
Sen-Banerjee S, Mir S, Lin Z, et al. Kruppel-like factor 2 as a novel mediator of
statin effects in endothelial cells. Circulation. 2005;112(5):720-726.
doi:10.1161/CIRCULATIONAHA.104.525774
Jain MK, Ridker PM. Anti-inflammatory effects of statins: clinical evidence and
basic mechanisms. Nat Rev Drug Discov. 2005;4(12):977-987.
doi:10.1038/nrd1901
Laufs U, La Fata V, Plutzky J, Liao JK. Upregulation of endothelial nitric oxide
synthase by HMG CoA reductase inhibitors. Circulation. 1998;97(12):1129-
doi:10.1161/01.cir.97.12.1129
Wang ST, Ho HJ, Lin JT, et al. Simvastatin-induced cell cycle arrest through
inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21
accumulation in hepatocellular carcinoma cells. Cell Death Dis. 2017; 8(2):
e2626.
Liang Z, Li W, et al. Simvastatin suppresses the DNA replication licensing
factor MCM7 and inhibits the growth of tamoxifen-resistant breast cancer cells.
Sci Rep. 2017; 7: 41776.
J, Zeki AA, Mirzaei N, et al. Mevalonate cascade inhibition by simvastatin
induces the intrinsic apoptosis pathway via depletion of isoprenoids in tumor
cells. Sci Rep. 2017; 7: 44841.
Porter KE, Naik J, Turner NA, Dickinson T, Thompson MM, London NJ.
Simvastatin inhibits human saphenous vein neointima formation via inhibition
of smooth muscle cell proliferation and migration. J Vasc Surg.
;36(1):150-157. doi:10.1067/mva.2002.122029
Jakobisiak M, Golab J. Statins can modulate effectiveness of antitumor
therapeutic modalities. Med Res Rev. 2010;30(1):102-135.
doi:10.1002/med.20162
Rikitake Y, Kawashima S, Takeshita S, et al. Anti-oxidative properties of
fluvastatin, an HMG-CoA reductase inhibitor, contribute to prevention of
atherosclerosis in cholesterol-fed rabbits. Atherosclerosis. 2001;154(1):87-96.
doi:10.1016/s0021-9150(00)00468-8
Guijarro C, Blanco-Colio LM, Ortego M, et al. 3-Hydroxy-3-methylglutaryl
coenzyme a reductase and isoprenylation inhibitors induce apoptosis of
vascular smooth muscle cells in culture. Circ Res. 1998;83(5):490-500.
doi:10.1161/01.res.83.5.490
Kochuparambil ST, Al-Husein B, Goc A, Soliman S, Somanath PR. Anticancer
efficacy of simvastatin on prostate cancer cells and tumor xenografts is
associated with inhibition of Akt and reduced prostate-specific antigen
expression. J Pharmacol Exp Ther. 2011;336(2):496-505.
doi:10.1124/jpet.110.174870
Chen MJ, Cheng AC, Lee MF, Hsu YC. Simvastatin induces G1 arrest by upregulating GSK3β and down-regulating CDK4/cyclin D1 and CDK2/cyclin E1 in
human primary colorectal cancer cells. J Cell Physiol. 2018;233(6):4618-4625.
doi:10.1002/jcp.26156
Zhong S, Zhang X, Chen L, Ma T, Tang J, Zhao J. Statin use and mortality in
cancer patients: Systematic review and meta-analysis of observational
studies. Cancer Treat Rev. 2015;41(6):554-567.
doi:10.1016/j.ctrv.2015.04.005
Cordes T, Metallo CM. Statins Limit Coenzyme Q Synthesis and Metabolically
Synergize with MEK Inhibition in Pancreatic Tumors. Cancer Res.
;80(2):151-152. doi:10.1158/0008-5472.CAN-19-3415
Joharatnam-Hogan N, Alexandre L, Yarmolinsky J, et al. Statins as Potential
Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating
Repurposed Drugs. Curr Oncol Rep. 2021;23(3):29. Published 2021 Feb 13.
doi:10.1007/s11912-021-01023-z
Guerra B, Recio C, Aranda-Tavío H, Guerra-Rodríguez M, García-Castellano
JM, Fernández-Pérez L. The Mevalonate Pathway, a Metabolic Target in
Cancer Therapy. Front Oncol. 2021;11:626971. Published 2021 Feb 25.
doi:10.3389/fonc.2021.626971
Mohammadkhani N, Gharbi S, Rajani HF, et al. Statins: Complex outcomes
but increasingly helpful treatment options for patients. Eur J Pharmacol.
;863:172704. doi:10.1016/j.ejphar.2019.172704
Fujiwara D, Tsubaki M, Takeda T, et al. Statins induce apoptosis through
inhibition of Ras signaling pathways and enhancement of Bim and p27
expression in human hematopoietic tumor cells. Tumour Biol.
;39(10):1010428317734947. doi:10.1177/1010428317734947
Beckwitt CH, Brufsky A, Oltvai ZN, Wells A. Statin drugs to reduce breast
cancer recurrence and mortality. Breast Cancer Res. 2018;20(1):144.
Published 2018 Nov 20. doi:10.1186/s13058-018-1066-z
Wang G, Cao R, Wang Y, et al. Simvastatin induces cell cycle arrest and
inhibits proliferation of bladder cancer cells via PPARγ signalling pathway. Sci
Rep. 2016;6:35783. Published 2016 Oct 25. doi:10.1038/srep35783
Rao PS, Rao US. Statins decrease the expression of c-Myc protein in cancer
cell lines. Mol Cell Biochem. 2021;476(2):743-755. doi:10.1007/s11010-020-
-2
Sodero AO, Barrantes FJ. Pleiotropic effects of statins on brain cells. Biochim
Biophys Acta Biomembr. 2020;1862(9):183340.
doi:10.1016/j.bbamem.2020.183340
Miyazawa Y, Sekine Y, Kato H, Furuya Y, Koike H, Suzuki K. Simvastatin UpRegulates Annexin A10 That Can Inhibit the Proliferation, Migration, and
Invasion in Androgen-Independent Human Prostate Cancer Cells. Prostate.
;77(4):337-349. doi:10.1002/pros.23273
Locke JA, Wasan KM, Nelson CC, Guns ES, Leon CG. Androgen-mediated
cholesterol metabolism in LNCaP and PC-3 cell lines is regulated through two
different isoforms of acyl-coenzyme A:Cholesterol Acyltransferase
(ACAT). Prostate. 2008;68(1):20-33. doi:10.1002/pros.20674
Krycer JR, Kristiana I, Brown AJ. Cholesterol homeostasis in two commonly
used human prostate cancer cell-lines, LNCaP and PC-3. PLoS One.
;4(12):e8496. Published 2009 Dec 30. doi:10.1371/journal.pone.0008496
Swyer GI. The cholesterol content of normal and enlarged prostates. Cancer
Res. 1942; 2:372–375.
Di Vizio D, Solomon KR, and Freeman MR (2008) Cholesterol and cholesterolrich membranes in prostate cancer: an update. Tumori 94:633–639.
Li YC, Park MJ, Ye SK, Kim CW, Kim YN. Elevated levels of cholesterol-rich
lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by
cholesterol-depleting agents. Am J Pathol. 2006;168(4):1107-1405.
doi:10.2353/ajpath.2006.050959
Karreth FA, Tuveson DA. Modelling oncogenic Ras/Raf signalling in the
mouse. Curr Opin Genet Dev. 2009;19(1):4-11. doi:10.1016/j.gde.2008.12.006
Ghosh-Choudhury N, Mandal CC, Ghosh-Choudhury N, Ghosh Choudhury G.
Simvastatin induces derepression of PTEN expression via NFkappaB to inhibit
breast cancer cell growth. Cell Signal. 2010;22(5):749-758.
doi:10.1016/j.cellsig.2009.12.010
Roudier E, Mistafa O, Stenius U. Statins induce mammalian target of
rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-
deficient cells to cytostatic drugs. Mol Cancer Ther. 2006;5(11):2706-2715.
doi:10.1158/1535-7163.MCT-06-0352
Sivaprasad U, Abbas T, Dutta A. Differential efficacy of 3-hydroxy-3-
methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer
cells. Mol Cancer Ther. 2006;5(9):2310-2316. doi:10.1158/1535-7163.MCT06-0175
Murtola TJ, Visakorpi T, Lahtela J, Syvälä H, Tammela TLj. Statins and
prostate cancer prevention: where we are now, and future directions. Nat Clin
Pract Urol. 2008;5(7):376-387. doi:10.1038/ncpuro1146
Murtola TJ, Pennanen P, Syvälä H, Bläuer M, Ylikomi T, Tammela TL. Effects
of simvastatin, acetylsalicylic acid, and rosiglitazone on proliferation of normal
and cancerous prostate epithelial cells at therapeutic concentrations. Prostate.
;69(9):1017-1023. doi:10.1002/pros.20951
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