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Stimulating effect of normal-dosing of fibrates on cell proliferation: word of warning.

Lipids in health and disease (2016-09-24)
Katerina Cizkova, Jana Steigerova, Jan Gursky, Jiri Ehrmann

Fibrates are widely used hypolipidemic drugs, which serve as ligand of peroxisome proliferator-activated receptor α (PPARα). Recently, they have also been considered as potential anticancer agents. We studied effect of fibrates treatment on cell proliferation, expression of CYP2J2 and concomitant changes in expression of cell cycle regulatory proteins in three different human cell lines: HEK293, HepG2, and HT-29. We used WST-1 viability test, western blot and immunocytochemistry for detection of proteins of interests and analysis of cell cycle. Our results showed that at lower concentrations of all tested fibrates, viability of all tested cell lines is increased, whereas at higher concentrations, repression is apparent. Unfortunately, the viability of tested cells is predominantly increased in a range of concentration which is reached in patient plasma. This phenomenon is accompanyed by elevation of CYP2J2, increased number of cyclin E-positive cells and decreased number of Cdc25A-positive cells in all tested cell lines, and elevated cyclin A expression in HepG2 and HT-29. These changes are concentration-dependent. We suppose that increased level of CYP2J2 could explain enhanced cell proliferation in lower concentration of fibrates. Based on our results, we suggested there is no anti-cancer effect of fibrates in tested carcinoma cell lines.

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