Research Article

The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells

Volume: 42 Number: 4 December 29, 2021
Münevver Yenigül , Emel Gencer Akcok *
EN

The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive and invasive malignancy with a poor diagnosis because of the resistance, relapse and limited therapy. Histone deacetylases (HDAC) are a class of enzyme that have important roles in epigenetic modulations. These enzymes are intensely studied and HDAC inhibitors are considered as potent anticancer agents in both solid tumors and hematological malignancies. HDAC inhibitors can affect and induce different mechanisms such as cell cycle arrest, differentiation, and cell death. In this study, we aim to investigate the cytotoxic effect of Tubastatin A, which is a selective HDAC6 inhibitor, on cholangiocarcinoma cell lines, TFK-1 and EGI-1, by MTT assay. Besides, it was aimed to examine the impact on colony formation potential of the cells. The effect of the inhibitor on cell cycle distribution was also examined by using flow cytometry. Tubastatin A has significantly decreased the colony formation and changed cell cycle progression. Taken together, our results suggest that Tubastatin A could be a potent inhibitor against cholangiocarcinoma. On the basis of these results, further mechanistic studies are required to elucidate the antineoplastic activity of Tubastatin A.

Keywords

Cholangiocarcinoma, Histonedeacetylase, Tubastatin A, HDAC inhibitors, HDAC6.

Project Number

217S660

References

  1. [1] Pant K., Peixoto E., Richard S. Gradilone, S. A., Role of Histone Deacetylases in Carcinogenesis: Potential Role in Cholangiocarcinoma, Cells, 9(3) (2020) 780.
  2. [2] Rizvi S., Gores G. J., Pathogenesis, diagnosis, and management of cholangiocarcinoma, Gastroenterology, 145(6) (2013) 1215-29.
  3. [3] Dawson M. A., Kouzarides T., Cancer epigenetics: From mechanism to therapy, Cell, 150(1) (2012) 12-27.
  4. [4] Weinhold B., Epigenetics: the science of change, Environ. Health Perspect., 114(3) (2006) 160-7.
  5. [5] Li Y., Seto E., HDACs and HDAC inhibitors in cancer development and therapy, Cold Spring Harb. Perspect. Med., 6(10) (2016) a026831.
  6. [6] Sriraks R., Limpaiboon T., Histone deacetylases and their inhibitors as potential therapeutic drugs for cholangiocarcinoma–cell line findings, Asian Pacific J. Cancer Prev., 14(4) (2013) 2503-2508.
  7. [7] Dokmanovic M., Clarke C., Marks P. A., Histone deacetylase inhibitors: Overview and perspectives, Molecular Cancer Research, 5(10) (2007) 981-989.
  8. [8] Hubbert C., Guardiola A., Shao R., Kawaguchi Y., Ito A., Nixon A., Yoshida M., Wang X. F., Yao T. P., HDAC6 is a microtubuleassociated deacetylase, Nature, 417(6887) (2002) 455-458.
  9. [9] Sakamoto K. M., Aldana-Masangkay G. I., The role of HDAC6 in cancer, Journal of Biomedicine and Biotechnology, 2011 (2011) 875824.
  10. [10] Gradilone S. A., Pisarello M. J., LaRusso N. F., Primary Cilia in Tumor Biology: The Primary Cilium as a Therapeutic Target in Cholangiocarcinoma, Curr. Drug Targets, 18(8) (2015) 958-963.
APA
Yenigül, M., & Gencer Akcok, E. (2021). The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells. Cumhuriyet Science Journal, 42(4), 775-780. https://izlik.org/JA98JK29KC
AMA
1.Yenigül M, Gencer Akcok E. The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells. CSJ. 2021;42(4):775-780. https://izlik.org/JA98JK29KC
Chicago
Yenigül, Münevver, and Emel Gencer Akcok. 2021. “The Therapeutic Potential of Targeting HDAC6 With Tubastatin A in TFK-1 and EGI-1 Cholangiocarcinoma Cells”. Cumhuriyet Science Journal 42 (4): 775-80. https://izlik.org/JA98JK29KC.
EndNote
Yenigül M, Gencer Akcok E (December 1, 2021) The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells. Cumhuriyet Science Journal 42 4 775–780.
IEEE
[1]M. Yenigül and E. Gencer Akcok, “The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells”, CSJ, vol. 42, no. 4, pp. 775–780, Dec. 2021, [Online]. Available: https://izlik.org/JA98JK29KC
ISNAD
Yenigül, Münevver - Gencer Akcok, Emel. “The Therapeutic Potential of Targeting HDAC6 With Tubastatin A in TFK-1 and EGI-1 Cholangiocarcinoma Cells”. Cumhuriyet Science Journal 42/4 (December 1, 2021): 775-780. https://izlik.org/JA98JK29KC.
JAMA
1.Yenigül M, Gencer Akcok E. The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells. CSJ. 2021;42:775–780.
MLA
Yenigül, Münevver, and Emel Gencer Akcok. “The Therapeutic Potential of Targeting HDAC6 With Tubastatin A in TFK-1 and EGI-1 Cholangiocarcinoma Cells”. Cumhuriyet Science Journal, vol. 42, no. 4, Dec. 2021, pp. 775-80, https://izlik.org/JA98JK29KC.
Vancouver
1.Münevver Yenigül, Emel Gencer Akcok. The therapeutic potential of targeting HDAC6 with Tubastatin A in TFK-1 and EGI-1 cholangiocarcinoma cells. CSJ [Internet]. 2021 Dec. 1;42(4):775-80. Available from: https://izlik.org/JA98JK29KC