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4-Hydroxycoumarin effects on both cellular and genetic characteristics of hepatocellular carcinoma cells
4-Hydroxycoumarin is an aromatic substance which is metabolized in liver and used as a therapeutic agent for various diseases. We aimed to determine the impact of 4-Hydroxycoumarin on HepG2 cells according to their viability, proliferation, adhesion and gene expression of cellular behavior parameters. Inhibitory concentration 50 (IC50) of 4-Hydroxycoumarin was detected on HepG2 cells. After determining the optimal time and concentration, the effect of 4-Hydroxycoumarin on viability, proliferation and adhesion of HepG2 cells were observed. Gene expressions of Ki-67, MMP-2, MMP-9 and piR-823 expression were determined by using Real Time-Polymerase Chain Reaction. IC50 value of 4-Hydroxycoumarin on HepG2 cells was 5 µM at the 48th hour (p < 0.001). 5 µM at the 48th hour of 4-Hydroxycoumarin caused to decrease of proliferation (p < 0.001) and viability of HepG2 cells (p < 0.001). Viability rate were supported by hematoxylin-eosin staining. Adhesion of cells increased on 4-Hydroxycoumarin treated cells compared to control (p < 0.001). While Ki-67 gene expression of 4-Hydroxycoumarin treated group decreased (p < 0.001); upregulation of MMP-2, MMP-9 and piR-823 expressions were determined in 4-Hydroxycoumarin treated group (p < 0.001). According to the cellular and genetic perspective, 4-Hydroxycoumarin might be useful to treat hepatocellular carcinoma. High adhesion and proliferation are the main characteristics of HepG2 cells, 4-Hydroxycoumarin treatment caused to lose these functions. The genetic markers of these characteristics also supported the same result. These are first findings about the effect of 4-Hydroxycoumarin on piR-823 and genes which are key features of cellular survival mechanisms.
Key words: 4-Hydroxycoumarin, Matrix metalloproteinase, piRNA, piR-823, Hepatocellular carcinoma
E-mail: cagri.oner maltepe.edu.tr
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