Open Access

Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment

  • Authors:
    • Hiroo Kuroki
    • Tsutomu Anraku
    • Akira Kazama
    • Yuko Shirono
    • Vladimir Bilim
    • Yoshihiko Tomita
  • View Affiliations

  • Published online on: November 20, 2020     https://doi.org/10.3892/ol.2020.12315
  • Article Number: 64
  • Copyright: © Kuroki et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histone deacetylases (HDACs) are enzymes that remove acetyl groups from histones and have attracted attention as potential targets for cancer therapy. Several small molecule inhibitors have been developed to target HDACs; however, clinical trials of pan‑HDAC inhibitors have found these types of inhibitors to be inefficient and to be relatively highly toxic. In the present study, the role of one HDAC isozyme, HDAC6, in urothelial cancer was investigated. Protein expression levels and subcellular localization of HDAC6 was identified in surgically resected bladder tumors using immunohistochemistry. The antitumor effects of 12 small molecule HDAC6 inhibitors were also examined in vitro using cultured urothelial cancer cells. The HDAC6 inhibitors decreased cell viability, with IC50 values in the low µM range, as low as 2.20 µM. HDACi D, E and F had the lowest IC50 values. HDAC6 has been previously reported to regulate programmed death‑ligand 1 (PD‑L1) and PD‑L1 expression was found to be a predictor of decreased overall survival time. There was no association between the protein expression level of HDAC6 and PD‑L1 in tumor tissues; however, HDAC6 inhibition by specific small molecule inhibitors resulted in decreased expression levels of membranous PD‑L1 in cultured urothelial cancer cell lines. The results suggested that inhibition of HDAC6 could be a promising novel approach for the treatment of urothelial cancer.

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Spandidos Publications style
Kuroki H, Anraku T, Kazama A, Shirono Y, Bilim V and Tomita Y: Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment. Oncol Lett 21: 64, 2021
APA
Kuroki, H., Anraku, T., Kazama, A., Shirono, Y., Bilim, V., & Tomita, Y. (2021). Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment. Oncology Letters, 21, 64. https://doi.org/10.3892/ol.2020.12315
MLA
Kuroki, H., Anraku, T., Kazama, A., Shirono, Y., Bilim, V., Tomita, Y."Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment". Oncology Letters 21.1 (2021): 64.
Chicago
Kuroki, H., Anraku, T., Kazama, A., Shirono, Y., Bilim, V., Tomita, Y."Histone deacetylase 6 inhibition in urothelial cancer as a potential new strategy for cancer treatment". Oncology Letters 21, no. 1 (2021): 64. https://doi.org/10.3892/ol.2020.12315