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

Result code in 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>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

<a href="/en/project/NT13112" target="_blank" >NT13112: Studies of anticancer effects of statins</a><br>

Continuities

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

Publication year

2015

Confidentiality

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