Antiproliferative effect of statins: Focus on statin transport into cancer cells in vitro

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F15%3A43901460" target="_blank" >RIV/60461373:22330/15:43901460 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Antiproliferative effect of statins: Focus on statin transport into cancer cells in vitro

Popis výsledku v původním jazyce

Statins, widely used in clinics for treatment of hypercholesterolemia and prevention of cardiovascular diseases, are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, which is the rate-limiting enzyme of the mevalonate pathway. Statins cause depletion of both the product, cholesterol, and its intermediates, farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, which are inevitable for proper cell signaling. The chemical nature of individual statins is very diverse, which causes significant differences in their transport across cellular membranes, and thus in their antiproliferative efficiency. So far, the detailed mechanism of their action has not been fully explained. The aim of the presented work was to study the antiproliferative potency of eight commercially available statins using three pancreatic cancer cell line models (MIA PaCa-2, CAPAN-2 and BxPC-3) and to compare their potency using cell models expressing organic anion-transporting polypeptides (OATPs), such as Hep G2 and HEK 293T cell lines. Further, we have studied the statin transport efficiency in MIA PaCa-2 and Hep G2 cells treated by individual statins in concentration and time dependent manner. For that purpose, ultrahigh pressure liquid chromatography together with tandem high resolution molecular spectroscopy (UHPLC-HRMS/MS) has been employed. In summary, we found that the action of individual statins strongly differed. Among the most potent ones in terms of antiproliferative effects in pancreatic cancer model belong cerivastatin, simvastatin and pitavastatin in cell lines without the OATPs expression. Contrary to that, OATP positive cells were very sensitive also to pravastatin.

Název v anglickém jazyce

Antiproliferative effect of statins: Focus on statin transport into cancer cells in vitro

Popis výsledku anglicky

Statins, widely used in clinics for treatment of hypercholesterolemia and prevention of cardiovascular diseases, are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, which is the rate-limiting enzyme of the mevalonate pathway. Statins cause depletion of both the product, cholesterol, and its intermediates, farnesyl-pyrophosphate and geranylgeranyl-pyrophosphate, which are inevitable for proper cell signaling. The chemical nature of individual statins is very diverse, which causes significant differences in their transport across cellular membranes, and thus in their antiproliferative efficiency. So far, the detailed mechanism of their action has not been fully explained. The aim of the presented work was to study the antiproliferative potency of eight commercially available statins using three pancreatic cancer cell line models (MIA PaCa-2, CAPAN-2 and BxPC-3) and to compare their potency using cell models expressing organic anion-transporting polypeptides (OATPs), such as Hep G2 and HEK 293T cell lines. Further, we have studied the statin transport efficiency in MIA PaCa-2 and Hep G2 cells treated by individual statins in concentration and time dependent manner. For that purpose, ultrahigh pressure liquid chromatography together with tandem high resolution molecular spectroscopy (UHPLC-HRMS/MS) has been employed. In summary, we found that the action of individual statins strongly differed. Among the most potent ones in terms of antiproliferative effects in pancreatic cancer model belong cerivastatin, simvastatin and pitavastatin in cell lines without the OATPs expression. Contrary to that, OATP positive cells were very sensitive also to pravastatin.

Druh

O - Ostatní výsledky

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

<a href="/cs/project/NT13112" target="_blank" >NT13112: Studium protinádorových účinků statinů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů