The similarity of selected statins – a comparative analysis

Dreyer, Constantin; Placha, Wojciech; Zagajewski, Jacek; Dygut, Jacek; Stangel-Wójcikiewicz, Klaudia; Piwowar, Monika

doi:10.1515/bams-2018-0034

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…Simvastatin, and not pravastatin, has been shown to inhibit the proliferation of oesophageal adenocarcinoma and squamous cell carcinoma cells [62]. It differs from other statins in its relatively high hydrophilicity [63]. Interestingly, a large randomized trial showed an increase in cancer incidence among elderly people treated with pravastatin [64] (a detailed meta-analysis and meta-regression analysis of randomized controlled trials was performed).…”

Section: Discussionmentioning

confidence: 99%

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma

Placha,

Suder,

Panek

et al. 2023

Biomolecules

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Despite the development of modern drugs, drug resistance in oncology remains the main factor limiting the curability of patients. This paper shows the use of a group of hydrophobic statins to inhibit drug resistance (Pgp protein). In a chemoresistance melanoma cell model, viability, necroptosis with DNA damage, the absorption of the applied pharmaceuticals, and the functional activity of the ABCB1 drug transporter after administration of docetaxel or docetaxel with a selected hydrophobic statin were studied. Taxol-resistant human melanoma cells from three stages of development were used as a model: both A375P and WM239A metastatic lines and radial growth phase WM35 cells. An animal model (Mus musculus SCID) was developed for the A375P cell line. The results show that hydrophobic statins administered with docetaxel increase the accumulation of the drug in the tumor cell a.o. by blocking the ABCB1 channel. They reduce taxol-induced drug resistance. The tumor size reduction was observed after the drug combination was administrated. It was shown that the structural similarity of statins is of secondary importance, e.g., pravastatin and simvastatin. Using cytostatics in the presence of hydrophobic statins increases their effectiveness while reducing their overall toxicity.

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Section: Discussionmentioning

confidence: 99%

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma

Placha,

Suder,

Panek

et al. 2023

Biomolecules

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show abstract

“…Elevated levels of TC and TG are strongly allied with CVD [10,119]. The discovery of statins takes pace and as of, some statins are on the market: atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin [120]. Many combinatorial preparations of statins and other agents, such as ezetimibe/simvastatin, are also in the market.…”

Section: Statins and Their Discoverymentioning

confidence: 99%

Oxidative Modification of Lipoproteins: A Potential Role of Oxidized Small dense LDL in Enhanced Atherogenicity

Alsaweed

2021

JPRI

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Atherosclerosis (AS) is a multifaceted inflammatory syndrome of the arterial wall to which number of mediators have been implicated in lesion progression. Triglyceride (TG)-rich lipoproteins consist of the large diversity of lipoprotein particles that fluctuate in density, size, and apolipoprotein composition. Two foremost phenotypes, on basis of size, chemical configuration, and density, of low-density-lipoprotein (LDL) have been recognized i.e., pattern A, having LDL diameter greater than 25.5nm (large buoyant LDL or lb-LDL) and pattern B, having LDL diameter less than or equal to 25.5nm (small-dense LDL or sd-LDL). Small-dense low-density-lipoprotein (sd-LDL) particles are produced by potential intravascular hydrolysis of TG-rich VLDL particles via lipoprotein lipases (LPLs), hepatic lipases (HLs) and cholesterol ester transfer protein (CETP). sd-LDL is more atherogenic due to its smaller size, increased penetration into the arterial wall, extended plasma half-life, lesser binding affinity for LDL receptors (LDL-R) as well as lower resistance to oxidative stress when equated with lb-LDL. The higher atherogenic potential of sd-LDL is due to its enhanced susceptibility to oxidation, owing to high polyunsaturated fatty acids (PUFA), low cholesterol and Apoprotein B (ApoB) content. An enhanced understanding of sd-LDL metabolism at the molecular level, transport and clearance may result in the development of sd-LDL as an independent predictive marker for AS events and may be used to maintain cholesterol homeostasis and prevent the succession of AS.

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“…The measurements were conducted at three different temperatures: 20, 25 and 37 • C. We chose representatives of both types of these drugs, based on some clear structural differences. We used two statins of type 1, namely pravastatin (hydroxy acid form) and simvastatin (lactone form), while we chose three statins of type 2, namely atorvastatin and rosuvastatin, because they are the most different from other statins in terms of chemical structure and physicochemical properties, and fluvastatin, which is highly similar to pitavastatin [60].…”

Section: Investigation Of Statin-hak1 Interactions Using Fluorescence Spectroscopymentioning

confidence: 99%

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies

Wujak

Kozakiewicz

Ciarkowska

et al. 2021

IJMS

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Statins are the most effective cholesterol-lowering drugs. They also exert many pleiotropic effects, including anti-cancer and cardio- and neuro-protective. Numerous nano-sized drug delivery systems were developed to enhance the therapeutic potential of statins. Studies on possible interactions between statins and human proteins could provide a deeper insight into the pleiotropic and adverse effects of these drugs. Adenylate kinase (AK) was found to regulate HDL endocytosis, cellular metabolism, cardiovascular function and neurodegeneration. In this work, we investigated interactions between human adenylate kinase isoenzyme 1 (hAK1) and atorvastatin (AVS), fluvastatin (FVS), pravastatin (PVS), rosuvastatin (RVS) and simvastatin (SVS) with fluorescence spectroscopy. The tested statins quenched the intrinsic fluorescence of hAK1 by creating stable hAK1-statin complexes with the binding constants of the order of 104 M−1. The enzyme kinetic studies revealed that statins inhibited hAK1 with significantly different efficiencies, in a noncompetitive manner. Simvastatin inhibited hAK1 with the highest yield comparable to that reported for diadenosine pentaphosphate, the only known hAK1 inhibitor. The determined AK sensitivity to statins differed markedly between short and long type AKs, suggesting an essential role of the LID domain in the AK inhibition. Our studies might open new horizons for the development of new modulators of short type AKs.

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The similarity of selected statins – a comparative analysis

Cited by 5 publications

References 14 publications

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma

The Blocking of Drug Resistance Channels by Selected Hydrophobic Statins in Chemoresistance Human Melanoma

Oxidative Modification of Lipoproteins: A Potential Role of Oxidized Small dense LDL in Enhanced Atherogenicity

Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies

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