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4-Hydroxycoumarin Effects on Both Cellular and Genetic Characteristics of Hepatocellular Carcinoma Cells

Abstract

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 48 h (p < 0.001). 5 μM at the 48 h 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.

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Funding

This study is funded by 2209-A Programme of the Scientific and Technological Research Council of Turkey (TÜBİTAK).

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The authors declare that they have no conflicts of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

AUTHORS CONTRIBUTION

All authors (Çağri Öner (ÇÖ), Dilara Soyergin (DS), Ahmet Özyurt (AÖ), Ertuğrul ÇOLAK (EÇ)) substantially contributed to the conception and design of the study, the acquisition of data, including conducting the experiments and analysis and interpretation of the results. They took part in interpreting the results statistically. Furthermore, they drafted the manuscript and critically revised it, approved the final version, and took responsibility for the statements made in the article.

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Öner, Ç., Soyergin, D., Özyurt, A. et al. 4-Hydroxycoumarin Effects on Both Cellular and Genetic Characteristics of Hepatocellular Carcinoma Cells. Cytol. Genet. 56, 292–300 (2022). https://doi.org/10.3103/S0095452722030094

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Keywords:

  • 4-Hydroxycoumarin
  • matrix metalloproteinase
  • piRNA
  • piR-823
  • hepatocellular carcinoma