Pitavastatin sodium

Pitavastatin (NK-104) sodium is a potent hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor. Pitavastatin sodium inhibits cholesterol synthesis from acetic acid with an IC50 of 5.8 nM in HepG2 cells. Pitavastatin sodium is an efficient hepatocyte low-density lipoprotein-cholesterol (LDL-C) receptor inducer. Pitavastatin sodium also possesses anti-atherosclerotic, anti-asthmatic, anti-osteoarthritis, antineoplastic, neuroprotective, hepatoprotective and reno-protective effects[1][2][3][8].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Metabolic Enzyme/Protease >> HMG-CoA Reductase (HMGCR)

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Autophagy >> Mitophagy

Research Areas >> Metabolic Disease

Research Areas >> Neurological Disease

HMG-CoA Reductase[1]

Pitavastatin inhibits the growth of a panel of ovarian cancer cells, including those considered most likely to represent HGSOC, grown as a monolayers (IC50=0.4-5 μM) or as spheroids (IC50 = 0.6-4 μM)[4].  Pitavastatin (1 μM; 48 hours) induces apoptosis, evidenced by the increased activity of executioner caspases-3,7 as well as caspase-8 and caspase-9 in Ovcar-8 cells and Ovcar-3 cells[4]. Pitavastatin (1 μM, 48 hours) causes PARP cleavage in Ovcar-8 cells[4]. Pitavastatin (0.1 and 1 μM; 1 h, then cells incubate with TNF-α for 6 h) increases the expression of ICAM-1 mRNA through suppressing NF-κB pathway in TNF-α-stimulated human saphenous vein endothelial cells[6]. Western Blot Analysis[4] Cell Line: Ovcar-8 cells Concentration: 1 μM Incubation Time: 48 hours Result: Induced PARP cleavage.

Pitavastatin (59 mg/kg; p.o.; twice daily for 28 days) causes significant tumour regression[4]. Pitavastatin (0.1 mg/kg; p.o; daily for 12 weeks) retards the progression of atherosclerosis formation and improves NO bioavailability by eNOS up-regulation and decrease of O2- in diet induced severe hyperlipidemia rabbit model[7]. Animal Model: 4 week old female NCR Nu/Nu female mice (bearing Ovcar-4 tumours)[4] Dosage: 59 mg/kg Administration: p.o.; twice daily for 28 days Result: Caused significant tumour regression. Animal Model: Female New Zealand white rabbits (diet induced severe hyperlipidemia)[7] Dosage: 0.1 mg/kg Administration: p.o; daily for 12 weeks Result: Retarded the progression of atherosclerosis formation and improved NO bioavailability by eNOS up-regulation and decrease of O2-.

[1]. Morikawa S, et al. Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. J Atheroscler Thromb. 2000;7(3):138-44.

[2]. Katsuki S, et al. Nanoparticle-mediated delivery of pitavastatin inhibits atherosclerotic plaque destabilization/rupture in mice by regulating the recruitment of inflammatory monocytes. Circulation. 2014 Feb 25;129(8):896-906.

[3]. Tajiri K, et al. Pitavastatin regulates helper T-cell differentiation and ameliorates autoimmune myocarditis in mice. Cardiovasc Drugs Ther. 2013 Oct;27(5):413-24.

[4]. Hamano T, et al. Pitavastatin decreases tau levels via the inactivation of Rho/ROCK. Neurobiol Aging. 2012 Oct;33(10):2306-20.

[5]. de Wolf E, et al.Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer.Sci Rep. 2017 Jul 14;7(1):5410.

[6]. Demir B, et al. The Effects of Pitavastatin on Nuclear Factor-Kappa B and ICAM-1 in Human Saphenous Vein Graft Endothelial Culture. Cardiovasc Ther. 2019 May 2;2019:2549432.

[7]. Hayashi T, et al. A new HMG-CoA reductase inhibitor, pitavastatin remarkably retards the progression of high cholesterol induced atherosclerosis in rabbits. Atherosclerosis. 2004 Oct;176(2):255-63.

[8]. Sahebkar A, et al. A comprehensive review on the lipid and pleiotropic effects of pitavastatin. Prog Lipid Res. 2021 Nov;84:101127.