Skip to main content
SpringerLink
Log in

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

  • Published:
Cytology and Genetics Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.

Similar content being viewed by others

REFERENCES

  1. Abraham, K., Wohrlin, F., Lindtner, O., et al., Toxicology and risk assessment of coumarin: Focus on human data, Mol. Nutr. Food Res., 2010, vol. 54, no. 2, pp. 228–239. https://doi.org/10.1002/mnfr.200900281

    Article  CAS  PubMed  Google Scholar 

  2. Bar-Ziv, R., Tlusty, T., Moses, E., et al., Pearling in cells: A clue to understanding cell shape, Proc. Natl. Acad. Sci. U. S. A., 1999, vol. 96, no. 18, pp. 10140–10145. https://doi.org/10.1073/pnas.96.18.10140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Breckenridge, A.M., Leck, J.B., Park, B.K., et al., J. Pharmacol., 1978, vol. 64, art. ID 399.

    Google Scholar 

  4. Bullwinkel, J., Baron-Luhr, B., Ludemann, A., et al., Ki-67 protein is associated with ribosomal RNA transcription in quiescent and proliferating cells, J. Cell. Physiol., 2006, vol. 206, no. 3, pp. 624–635. https://doi.org/10.1002/jcp.20494

    Article  CAS  PubMed  Google Scholar 

  5. Chalbatani, G.M., Dana, H., Memari, F., et al., Biological function and molecular mechanism of piRNA in cancer, Pract. Lab. Med., 2019, vol. 13, art. ID e00113. https://doi.org/10.1016/j.plabm.2018.e00113

    Article  PubMed  Google Scholar 

  6. Chen, W.C., Liu, L., Shen, Y.F., et al., A new coumarin derivative plays a role in rhabdoviral clearance by interfering glycoprotein function during the early stage of viral infection, Cell. Signaling, 2018, vol. 51, pp. 199–210. https://doi.org/10.1016/j.cellsig.2018.08.007

    Article  CAS  Google Scholar 

  7. Cheng, J., Deng, H.X., Xiao, B.X., et al., piR-823, a novel non-coding small RNA, demonstrates in vitro and in vivo tumor suppressive activity in human gastric cancer cells, Cancer Lett., 2012, vol. 315, pp. 12–17. https://doi.org/10.1016/j.canlet.2011.10.004

    Article  CAS  PubMed  Google Scholar 

  8. Chien, Y.C., Liu, L.C., Ye, H.Y., et al., EZH2 promotes migration and invasion of triple-negative breast cancer cells via regulating TIMP2-MMP-2/-9 pathway, Am. J. Cancer Res., 2018, vol. 8, no. 3, pp. 422–434.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Cui, J., Dong, B.W., Liang, P., et al., Effect of c-myc, Ki-67, MMP-2 and VEGF expression on prognosis of hepatocellular carcinoma patients undergoing tumor resection, World J. Gastroenterol., 2004, vol. 10, pp. 1533–1536. https://doi.org/10.3748/wjg.v10.i10.1533

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cui, L., Lou, Y., Zhang, X., et al., Detection of circulating tumor cells in peripheral blood from patients with gastric cancer using piRNAs as markers, Clin. Biochem., 2011, vol. 44, no. 13, pp. 1050–1057. https://doi.org/10.1016/j.clinbiochem.2011.06.004

    Article  CAS  PubMed  Google Scholar 

  11. Dehn, P.F., White, C.M., Conners, D.E., et al., Characterization of the human hepatocellular carcinoma (hepg2) cell line as an in vitro model for cadmium toxicity studies, In Vitro Cell. Dev. Biol.: Anim., 2004, vol. 40, nos. 5–6, pp. 172–182. https://doi.org/10.1290/1543-706X(2004)40<172:COTHHC>2.0.CO;2

    Article  CAS  Google Scholar 

  12. Deryugina, E.I. and Quigley, J.P., Matrix metalloproteinases and tumor metastasis, Cancer Metastasis Rev., 2006, vol. 25, pp. 9–34. https://doi.org/10.1007/s10555-006-7886-9

    Article  CAS  PubMed  Google Scholar 

  13. Dowsett, M., Nielsen, T.O., A’hern, R., et al., Assessment of Ki67 in breast cancer: Updated recommendations from the International Ki67 in Breast Cancer working group, J. Natl. Cancer Inst., 2011, vol. 103, no. 7, pp. 1656–1664. https://doi.org/10.1093/jnci/djr393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Egan, D., James, P., Cooke, D., et al., Studies on the cytostatic and cytotoxic effects and mode of action of 8-nitro-7-hydroxycoumarin, Cancer Lett., 1997, vol. 118, no. 2, pp. 201–211. https://doi.org/10.1016/s0304-3835(97)00331-5

    Article  CAS  PubMed  Google Scholar 

  15. El-Serag, H.B. and Rudolph, K.L., Hepatocellular carcinoma: epidemiology and molecular carcinogenesis, Gastroenterology, 2007, vol. 132, no. 7, pp. 2557–2576. https://doi.org/10.1053/j.gastro.2007.04.061

    Article  CAS  PubMed  Google Scholar 

  16. Emami, S. and Dadashpour, S., Current developments of coumarin-based anti-cancer agents in medicinal chemistry, Eur. J. Med. Chem., 2015, vol. 102, pp. 611–630. https://doi.org/10.1016/j.ejmech.2015.08.033

    Article  CAS  PubMed  Google Scholar 

  17. Finn, G.J., Creaven, B., and Egan, D.A., Study of the in vitro cytotoxic potential of natural and synthetic coumarin derivatives using human normal and neoplastic skin cell lines, Melanoma Res., 2001, vol. 11, pp. 461–467.

    Article  CAS  Google Scholar 

  18. Funaya, C., Antony, C., Sachidanandam, R., et al., Miwi catalysis is required for piRNA amplification‑independent LINE1 transposon silencing, Nature, 2011, vol. 480, pp. 264–267.

    Article  Google Scholar 

  19. Gu, J., Li, Y., Fan, L., et al., Identification of aberrantly expressed long non-coding RNAs in stomach adenocarcinoma, Oncotarget, 2017, vol. 8, pp. 49201–49216. https://doi.org/10.18632/oncotarget.17329

    Article  PubMed  PubMed Central  Google Scholar 

  20. Han, H., Zhang, Z.-F., Zhang, J.-F., et al., Novel coumarin derivatives: Synthesis, anti-breast cancer activity and docking study, Main Group Chem., 2019, vol. 18, pp. 71–79. https://doi.org/10.3233/mgc-180682

    Article  CAS  Google Scholar 

  21. Iliev, R., Stanik, M., Fedorko, M., et al., Decreased expression levels of PIWIL1, PIWIL2, and PIWIL4 are associated with worse survival in renal cell carcinoma patients, OncoTargets Ther., 2016, vol. 9, pp. 217–222. https://doi.org/10.2147/OTT.S91295

    Article  CAS  Google Scholar 

  22. Ingber, D.E., Tensegrity II. How structural networks influence cellular information processing networks, J. Cell Sci., 2003, vol. 116, no. 8, pp. 1397–1408. https://doi.org/10.1242/jcs.00360

    Article  CAS  PubMed  Google Scholar 

  23. Jacobs, D.I., Qin, Q., Lerro, M.C., et al., PIWI-interacting RNAs in gliomagenesis: evidence from post-GWAS and functional analyses, Cancer Epidemiol., Biomarkers Prev., 2016, vol. 25, no. 7, pp. 1073–1080. https://doi.org/10.1158/1055-9965.EPI-16-0047

    Article  CAS  Google Scholar 

  24. Jimenez-Orozco, F.A., Lopez-Gonzalez, J.S., Nieto-Rodriguez, A., et al., Decrease of cyclin D1 in the human lung adenocarcinoma cell line A-427 by 7-hydroxycoumarin, Lung Cancer, 2001, vol. 34, no. 2, pp. 185–194.

    Article  CAS  Google Scholar 

  25. Zanker, K.S., Blumel, J., Lange, J.R., et al., Coumarin in melanoma patients: an experimental and clinical study, Drugs Exp. Clin. Res., 1984, vol. 10, pp. 767–774.

    Google Scholar 

  26. Kawaii, S., Tomono, Y., Ogawa, K., et al., The antiproliferative effect of coumarins on several cancer cell lines, Anticancer Res., 2001, vol. 21, pp. 917–923.

    CAS  PubMed  Google Scholar 

  27. Keating, J.G. and O’kennedy, R., The Chemistry and Occurrence of Coumarins, New York: Wiley, 1997.

    Google Scholar 

  28. King, K.L., Hwang, J.J., Chau, G.Y., et al., Ki-67 expression as a prognostic marker in patients with hepatocellular carcinoma, J. Gastroenterol. Hepatol., 1998, vol. 13, pp. 273–279. https://doi.org/10.1111/j.1440-1746.1998.01555.x

    Article  CAS  PubMed  Google Scholar 

  29. Kokron, O., Maca, S., Gasser, G., et al., Cimetidine and coumarin therapy of renal-cell carcinoma, Oncology, 1991, vol. 48, pp. 102–126.

    Article  CAS  Google Scholar 

  30. Lake, B.G., Coumarin metabolism, toxicity and carcinogenicity: relevance for human risk assessment, Food Chem. Toxicol., 1999, vol. 37, pp. 423–453.

    Article  CAS  Google Scholar 

  31. Li, J., Xue, X.Y., Li, X., et al., Synthesis of biscoumarin and dihydropyran derivatives as two novel classes of potential anti-bacterial derivatives, Arch. Pharmacal Res., 2016, vol. 39, pp. 1349–1355. https://doi.org/10.1007/s12272-015-0614-7

    Article  CAS  Google Scholar 

  32. Lirdprapamongkol, K., Kramb, J.P., Suthiphongchai, T., et al., Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo, J. Agric. Food Chem., 2009, vol. 57, pp. 3055–3063. https://doi.org/10.1021/jf803366f

    Article  CAS  PubMed  Google Scholar 

  33. Liu, Y., Dou, M., Song, X., et al., The emerging role of the piRNA/piwi complex in cancer, Mol. Cancer, 2019, vol. 18, art. ID 123. https://doi.org/10.1186/s12943-019-1052-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Lopez-Gonzalez, J.S., Prado-Garcia, H., Aguilar-Cazares, D., et al., Apoptosis and cell cycle disturbances induced by coumarin and 7-hydroxycoumarin on human lung carcinoma cell lines, Lung Cancer, 2004, vol. 43, pp. 275–283. https://doi.org/10.1016/j.lungcan.2003.09.005

    Article  PubMed  Google Scholar 

  35. Man, S.L., Gao, W.Y., Zhang, Y.J., et al., Formosanin C‑inhibited pulmonary metastasis through repression of matrix metalloproteinases on mouse lung adenocarcinoma, Cancer Biol. Ther., 2011, vol. 11, pp. 592–598. https://doi.org/10.4161/cbt.11.6.14668

    Article  CAS  PubMed  Google Scholar 

  36. Marshall, M.E., Butler, K., and Fried, A., Phase I evaluation of coumarin (1,2-benzopyrone) and cimetidine in patients with advanced malignancies, Mol. Biother., 1991, vol. 3, no. 3, pp. 170–178.

    CAS  PubMed  Google Scholar 

  37. Marshall, M.E., Kervin, K., Benefield, C., et al., Growth-inhibitory effects of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin on human malignant cell lines in vitro, J. Cancer Res. Clin. Oncol., 1994, vol. 120, pp. S3–S10.

    Article  CAS  Google Scholar 

  38. Marusyk, A., Tabassum, D.P., Altrock, P.M., et al., Non-cell-autonomous driving of tumour growth supports sub-clonal heterogeneity, Nature, 2014, vol. 514, pp. 54–58. https://doi.org/10.1038/nature13556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Mohler, J.L., Gomella, L.G., Crawford, E.D., et al., Phase II evaluation of coumarin (1,2-benzopyrone) in metastatic prostatic carcinoma, Prostate, 1992, vol. 20, no. 2, pp. 123–131.

    Article  CAS  Google Scholar 

  40. Mohler, J.L., Williams, B.T., Thompson, I.M., et al., Coumarin (1,2-benzopyrone) for the treatment of prostatic carcinoma, J. Cancer Res. Clin. Oncol., 1994, vol. 120, pp. S35–S38.

    Article  Google Scholar 

  41. Mosmann, T., Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods, 1983, vol. 65, nos. 1–2, pp. 55–63. https://doi.org/10.1016/0022-1759(83)90303-4

    Article  CAS  PubMed  Google Scholar 

  42. Nasr, T., Bondock, S., and Youns, M., Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives, Eur. J. Med. Chem., 2014, vol. 76, pp. 539–548. https://doi.org/10.1016/j.ejmech.2014.02.026

    Article  CAS  PubMed  Google Scholar 

  43. Öner, C., Turgut Coşan, D., and Çolak, E., Estrogen and androgen hormone levels modulate the expression of PIWI interacting RNA in prostate and breast cancer, PLoS One, 2016, vol. 11, art. ID e0159044. https://doi.org/10.1371/journal.pone.0159044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ozata, D.M., Gainetdinov, I., Zoch, A., et al., PIWI-interacting RNAs: small RNAs with big functions, Nat. Rev. Genet., 2019, vol. 20, pp. 89–108. https://doi.org/10.1038/s41576-018-0073-3

    Article  CAS  PubMed  Google Scholar 

  45. Phillips, C., Zeringue, A.L., Mcdonald, J.R., et al., Tumor necrosis factor inhibition and head and neck cancer recurrence and death in rheumatoid arthritis, PLoS One, 2015, vol. 10, art. ID e0143286. https://doi.org/10.1371/journal.pone.0143286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rennenberg, R.J., Van Varik, B.J., Schurgers, L.J., et al., Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans, Blood, 2010, vol. 115, no. 24, pp. 5121–5123. https://doi.org/10.1182/blood-2010-01-264598

    Article  CAS  PubMed  Google Scholar 

  47. Salinas-Jazmin, N., De La Fuente, M., Jaimez, R., et al., Antimetastatic, antineoplastic, and toxic effects of 4-hydroxycoumarin in a preclinical mouse melanoma model, Cancer Chemother. Pharmacol., 2010, vol. 65, pp. 931–940. https://doi.org/10.1007/s00280-009-1100-z

    Article  CAS  PubMed  Google Scholar 

  48. Shokoohinia, Y., Hosseinzadeh, L., Alipour, M., et al., Comparative evaluation of cytotoxic and apoptogenic effects of several coumarins on human cancer cell lines: Osthole induces apoptosis in p53-deficient H1299 cells, Adv. Pharmacol. Sci. 2014, art. ID 847574.

  49. Sobecki, M., Mrouj, K., Colinge, J., et al., Cell-Cycle regulation accounts for variability in Ki-67 expression levels, Cancer Res., 2017, vol. 77, no. 10, pp. 2722–2734. https://doi.org/10.1158/0008-5472.CAN-16-0707

    Article  CAS  PubMed  Google Scholar 

  50. Stefanova, T.H., Nikolova, N.J., Toshkova, R.A., et al., Antitumor and immunomodulatory effect of coumarin and 7-hydroxycoumarin against Sarcoma 180 in mice, J. Exp. Ther. Oncol., 2007, vol. 6, no. 2, pp. 107–115.

    CAS  PubMed  Google Scholar 

  51. Thornes, R.D., Daly, L., Lynch, G., et al., Treatment with coumarin to prevent or delay recurrence of malignant melanoma, J. Cancer Res. Clin. Oncol., 1994, vol. 120, pp. S32–S34.

    Article  Google Scholar 

  52. Ujjin, P., Satarug, S., Vanavanitkun, Y., et al., Variation in coumarin 7-hydroxylase activity associated with genetic polymorphism of cytochrome P450 2A6 and the body status of iron stores in adult Thai males and females, Pharmacogenetics, 2002, vol. 12, no. 3 pp. 241–249.

    Article  CAS  Google Scholar 

  53. Vázquez, R., Riveiro, M.E., Vermeulen, M., et al., Structure-anti-leukemic activity relationship study of ortho-dihydroxycoumarins in U-937 cells: key role of the δ-lactone ring in determining differentiation-inducing potency and selective pro-apoptotic action, Bioorg. Med. Chem., 2012, vol. 20, pp. 5537–5549.

    Article  Google Scholar 

  54. Velasco-Velazquez, M.A., Agramonte-Hevia, J., Barrera, D., et al., 4-Hydroxycoumarin disorganizes the actin cytoskeleton in B16–F10 melanoma cells but not in B82 fibroblasts, decreasing their adhesion to extracellular matrix proteins and motility, Cancer Lett., 2003, vol. 198, pp. 179–186. https://doi.org/10.1016/S0304-3835(03)00333-1

    Article  CAS  PubMed  Google Scholar 

  55. Velasco-Velázquez, M.A., Salinas-Jazmín, N., Mendoza-Patiño, N., et al., Reduced paxillin expression contributes to the antimetastatic effect of 4-hydroxycoumarin on B16-F10 melanoma cells, Cancer Cell. Int., 2008, art. ID 8.

  56. Vianna, D.R., Hamerski, L., Figueiro, F., et al., Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species, Eur. J. Med. Chem., 2012, vol. 57, pp. 268–274. https://doi.org/10.1016/j.ejmech.2012.09.007

    Article  CAS  PubMed  Google Scholar 

  57. Wu, X.Q., Huang, C., Jia, Y.M., et al., Novel coumarin-dihydropyrazole thio-ethanone derivatives: Design, synthesis and anticancer activity, Eur. J. Med. Chem., 2014, vol. 74, pp. 717–725. https://doi.org/10.1016/j.ejmech.2013.06.014

    Article  CAS  PubMed  Google Scholar 

  58. Xiao, Z., Shen, J., Zhang, L., et al., Therapeutic targeting of noncoding RNAs in hepatocellular carcinoma: Recent progress and future prospects (Review), Oncol. Lett., 2018, vol. 15, pp. 3395–3402. https://doi.org/10.3892/ol.2018.7758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Xu, C., Rao, Y.S., Xu, B., et al., An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles, Biochem Biophys. Res. Commun., 2002, vol. 290, no. 1, pp. 318–324. https://doi.org/10.1006/bbrc.2001.6209

    Article  CAS  PubMed  Google Scholar 

  60. Yamashiro, H. and Siomi, M.C., PIWI-interacting RNA in Drosophila: Biogenesis, transposon regulation, and beyond., Chem. Rev., 2018, vol. 118, no. 8, pp. 4404–4421. https://doi.org/10.1021/acs.chemrev.7b00393

    Article  CAS  PubMed  Google Scholar 

  61. Yan, H., Wu, Q.L., Sun, C.Y., et al., piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma, Leukemia, 2015, vol. 29, pp. 196–206. https://doi.org/10.1038/leu.2014.135

    Article  CAS  PubMed  Google Scholar 

  62. Yang, Y., Lu, N., Zhou, J., et al., Cyclophilin A up-regulates MMP-9 expression and adhesion of monocytes/macrophages via CD147 signalling pathway in rheumatoid arthritis, Rheumatology (Oxford), 2008, vol. 47, no. 9, pp. 1299–1310. https://doi.org/10.1093/rheumatology/ken225

    Article  CAS  PubMed  Google Scholar 

  63. Yin, J., Jiang, X.Y., Qi, W., et al., piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1, Cancer Sci., 2017, vol. 108, no. 9, pp. 1746–1756. https://doi.org/10.1111/cas.13300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhang, J., Zhang, D., Wu, G-Q., et al., Propofol inhibits the adhesion of hepatocellular carcinoma cells by upregulating microRNA-199a and downregulating MMP-9 expression, Hepatobiliary Pancreatic Dis. Int., 2013, vol. 12, pp. 305–309. https://doi.org/10.1016/s1499-3872(13)60048-x

    Article  CAS  Google Scholar 

Download references

Funding

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

Author information

Authors and Affiliations

  1. Maltepe University, Medical Faculty, Department of Medical Biology and Genetics, İstanbul, Turkey

    Çağri Öner

  2. Maltepe University, Medical Faculty, İstanbul, Turkey

    Dilara Soyergin & Ahmet Özyurt

  3. Eskişehir Osmangazi University, Medical Faculty, Department of Biostatistics, Eskişehir, Turkey

    Ertuğrul Çolak

Authors
  1. Çağri Öner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dilara Soyergin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmet Özyurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ertuğrul Çolak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Çağri Öner.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

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.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0095452722030094

Keywords:

Search

Navigation