The effect of fibrates on cell viability

Konference: 2015 11. sympózium molekulovej patológie s medzinárodnou účasťou a Martinské dni nelekárskych pracovníkov v patológii

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Posterová sekcia

Číslo abstraktu: p04

Autoři: Mgr. Kateřina Čížková; Mgr. Jana Steigerová, Ph.D.; Prof. MUDr. Jiří Ehrmann jr., Ph.D.

Fibrates are clinically widely used drugs for treatment of dislipidemias. Moreover, there are a lot of studies describing their potential for can­cer treatment and chemoprevention. That's why we studied effect of fenofibrate, bezafibrate and gemfibrozil on cell proliferation in three different human cell lines: one nontumorous cell line HEK293 (human embryonic kidney), and two carcinoma cell lines HepG2 (hepatocellular carcinoma), and HT-29 (human colorectal adenocarcinoma) by WST-1 cell proliferation assay. Our results show that at lower concentrations of all tested fibrates, viability of all tested cell lines is increased, whereas at higher concentrations, repression is apparent. Then we studied changes in expression of cell cycle regula- tory proteins by immunocytochemistry. Our results shows increased number of cells expressing cyclin E and decreased number of cells expressing Cdc25A in all tested cell lines. Moreover, in HepG2 and HT-29 cell lines, cyclin A was elevated too. These effects are concentration-dependent. Cyclin E and cyclin A are regulators of late G1 and S phases of cell cycle. Both of these cyclins bind to cyclin-dependent kinase 2 (CDK2). For activation of these complexes, dephosporylation by Cdc25A is required. Although it has been described that Cdc25A downregulati- on is enough for cell cycle arresting, we suppose that at maximum viability concentrations, Cdc25A downregulation is not sufficient for this effect. We suggest that fibrates could have benefical effects only in treatment of certain types of tumours (as described in literature) however these effects are probably not general. Thus, their potential usage for cancer treatment should be considered carefully.

Datum přednesení příspěvku: 4. 6. 2016