Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line

Authors

  • Masumeh Sanaei Research center for non-communicable diseases, Jahrom University of medical sciences, Jahrom, Iran
  • Fraidoon Kavoosi Research center for non-communicable diseases https://orcid.org/0000-0001-7761-7912
  • Hossein Karami Student of Research Committee, Jahrom University of medical sciences, Jahrom, Iran

DOI:

https://doi.org/10.1590/s2175-97902020000419033

Keywords:

Trichostatin A. FHIT. WWOX. Apoptosis. Cancer.

Abstract

Previously, we evaluated the effect of trichostatin A (TSA) on the expression of DNA methyltransferase 1 (DNMT1) in Hepatocellular Carcinoma (HCC). Fragile histidine triad (FHIT) and WW domaincontaining oxidoreductase (WWOX) are two of the most common down-regulated genes in many cancers located on chromosome 3p14.2 and 16q23.3–24.1 respectively. The aim of the current study was to assess the effect of TSA on these genes expression, cell growth, and apoptosis in HCC WCH 17 cell. The cells were seeded and treated with TSA at different times. Then, MTT assay, flow cytometry, and qRT-PCR were achieved to determine viability, apoptosis and gene expression respectively. Cell growth was significantly inhibited, 92 to 36% after 24 h, 86 to 28% after 48 h, and 78 to 24% after 72 h. The results of flow cytometry confirmed that TSA increased apoptosis compared to the control group, the apoptosis percentage increased to 12%, 16%, and 18% in comparison to control groups (2%). Significant up-regulation of the genes was observed in all treated groups. We concluded that reexpression of silenced WWOX and FHIT genes could be achieved by TSA resulting in cell growth inhibition and apoptosis induction in WCH 17 cell.

Downloads

Download data is not yet available.

References

Cantor JP, Iliopoulos D, Rao AS, Druck T, Semba S, Han SY, et al. Epigenetic modulation of endogenous tumor suppressor expression in lung cancer xenografts suppresses tumorigenicity. Int J Cancer. 2007;120(1):24-31.

Ceccacci E, Minucci S. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia. Br J Cancer. 2016;114(6):605-611.

Chiba T, Yokosuka O, Fukai K, Kojima H, Tada M, Arai M, et al. Cell growth inhibition and gene expression induced by the histone deacetylase inhibitor, trichostatin A, on human hepatoma cells. Oncology. 2004;66(6):481-91.

Del Mare S, Salah Z, Aqeilan RI. WWOX: its genomics, partners, and functions. J Cell Biochem. 2009;108(4):737-45.

Glozak M, Seto E. Histone deacetylases and cancer. Oncogene. 2007;26(37):5420-32.

He D, Zhang Y-w, Zhang N-n, Zhou L, Chen J-n, Jiang Y, Shao C-k. Aberrant gene promoter methylation of p16, FHIT, CRBP1, WWOX, and DLC-1 in Epstein-Barr virus-associated gastric carcinomas. Med Oncol. 2015;32(4):92.

Iliopoulos D, Fabbri M, Druck T, Qin HR, Han S-Y, Huebner K. Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression. Clin Cancer Res. 2007;13(1):268-74.

Karras JR, Schrock MS, Batar B, Huebner K. Fragile genes that are frequently altered in cancer: players not passengers. Cytogenet Genome Res. 2016;150(3-4):208-16.

Kim H-J, Bae S-C. Histone deacetylase inhibitors: molecular mechanisms of action and clinical trials as anti-cancer drugs. Am J Transl Res. 2011;3(2):166-79.

Lai Y-CC, Cheng C-C, Lai Y-S, Liu Y-H. Cytokeratin 18-associated Histone 3 Modulation in Hepatocellular Carcinoma: A Mini Review. Cancer Genomics-Proteomics. 2017;14(4):219-23.

Wang Li, Chenggang D, Zhiqiang M, Lin G, Tao H. Effect of trichostatin a on fhit gene expression in human hepatoma cell line HEPG2. J Luzhou Med College. 2011;(4):352-355.

Lin J-T, Li H-Y, Chang N-S, Lin C-H, Chen Y-C, Lu P-J. WWOX suppresses prostate cancer cell progression through cyclin D1-mediated cell cycle arrest in the G1 phase. Cell Cycle. 2015;14(3):408-16.

Liu L, Li C, Yang D, Sun N, Xia W, editors. Trichostatin A affects breast cancer cell viability by modulating Fhit and Survivin expression. Biomedical Engineering and Biotechnology (iCBEB), 2012 International Conference on; 2012: IEEE.

Maeda N, Semba S, Nakayama S, Yanagihara K, Yokozaki H. Loss of WW domain-containing oxidoreductase expression in the progression and development of gastric carcinoma: clinical and histopathologic correlations. Virchows Archiv. 2010;457(4):423-32.

Midorikawa Y, Yamamoto S, Tsuji S, Kamimura N, Ishikawa S, Igarashi H, et al. Allelic imbalances and homozygous deletion on 8p23. 2 for stepwise progression of hepatocarcinogenesis. Hepatology. 2009;49(2):513-22.

Okumura H, Ishii H, Pichiorri F, Croce CM, Mori M, Huebner K. Fragile gene product, Fhit, in oxidative and replicative stress responses. Cancer Sci. 2009;100(7):1145-50.

Park S, Ludes-Meyers J, Zimonjic D, Durkin M, Popescu N, Aldaz C. Frequent downregulation and loss of WWOX gene expression in human hepatocellular carcinoma. Br J Cancer. 2004;91(4):753-759.

Qin HR, Iliopoulos D, Semba S, Fabbri M, Druck T, Volinia S, et al. A role for the WWOX gene in prostate cancer. Cancer Res. 2006;66(13):6477-81.

Ropero S, Esteller M. The role of histone deacetylases (HDACs) in human cancer. Mol Oncol. 2007;1(1):19-25.

Sanaei M, Kavoosi F. Effect of Curcumin and Trichostatin A on the Expression of DNA Methyltransfrase 1 in Hepatocellular Carcinoma Cell Line Hepa 16. Iranian J Pediatric Hematology Oncology. 2018;8(4):193-201.

Semba S, Trapasso F, Fabbri M, McCorkell K, Volinia S, Druck T, et al. Fhit modulation of the Akt-survivin pathway in lung cancer cells: Fhit-tyrosine 114 (Y114) is essential. Oncogene. 2006;25(20):2860-72.

Shanmugam MK, Arfuso F, Arumugam S, Chi-nnathambi A, Jinsong B, Warrier S, et al. Role of novel histone modifications in cancer. Oncotarget. 2018;9(13):11414-26.

Wahid B, Ali A, Rafique S, Idrees M. New insights into the epigenetics of hepatocellular carcinoma. BioMed Res Int; 2017;2017:1-16.

Wang L, Liu X-y, Gong S. Effect of TSA on the expression of FHIT in the human hepatoma cell line HepG2. Chongqing Medicine. 2010;15:1954-6.

Xu W, Parmigiani R, Marks P. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene. 2007;26(37):5541-52.

Yan H-C, Zhang J. Effects of sodium valproate on the growth of human ovarian cancer cell line HO8910. Asian Pac J Cancer Prev. 2012;13(12):6429-33.

Yuan B-Z, Keck-Waggoner C, Zimonjic DB, Thorgeirsson SS, Popescu NC. Alterations of the FHIT gene in human hepatocellular carcinoma. Cancer Res. 2000;60(4):1049-53.

Downloads

Published

2022-11-09

Issue

Section

Original Article

How to Cite

Effects of trichostatin A on FHIT and WWOX genes expression, cell growth inhibition and apoptosis induction in hepatocellular carcinoma WCH 17 cell line. (2022). Brazilian Journal of Pharmaceutical Sciences, 57. https://doi.org/10.1590/s2175-97902020000419033