Temozolomide-resistant glioblastoma depends on HDAC6 activity through regulation of DNA mismatch repair

Go Woon Kim, Dong Hoon Lee, Soo Keun Yeon, Yu Hyun Jeon, Jung Yoo, Sang Woo Lee, So Hee Kwon

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background/Aim: Histone deacetylase 6 (HDAC6) is considered as one of the most promising targets in drug development for cancer therapy. Drug resistance is a major cause of treatment failure in many cancers including glioblastoma (GBM), the most lethal malignant tumor. The role of HDAC6 in GBM resistance and its underlying mechanisms have not been well elucidated. Herein, we investigated the function of HDAC6 in modulating GBM resistance. Materials and Methods: The anticancer effects of four structurally distinct selective HDAC6 inhibitors were addressed using western blot, flow cytometry, CCK-8 assay, and CI in temozolomide (TMZ)-resistant GBM cells. Results: We showed that HDAC6-selecitve inhibitors block activation of the EGFR and p53 pathways in TMZ-resistant GBM cells. Importantly, the inhibition of HDAC6 correlates with increased levels of MSH2 and MSH6, key DNA mismatch repair proteins, in TMZ-resistant GBM cells. In addition to the MSH, HDAC6 inhibitors decrease MGMT expression in TMZ-resistant GBM cells. Furthermore, HDAC6 inhibitors increase TMZ sensitivity and efficiently induce apoptosis in TMZ-resistant GBM cells. Conclusion: Selective inhibition of HDAC6 may be a promising strategy for the treatment of TMZ-resistant GBM.

Original languageEnglish
Pages (from-to)6731-6741
Number of pages11
JournalAnticancer research
Issue number12
Publication statusPublished - 2019

Bibliographical note

Publisher Copyright:
© 2019 International Institute of Anticancer Research. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


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