Combination of acy-241 and jq1 synergistically suppresses metastasis of hnscc via regulation of mmp-2 and mmp-9

Ha Young Cho, Sang Wu Lee, Yu Hyun Jeon, Dong Hoon Lee, Go Woon Kim, Jung Yoo, So Yeon Kim, So Hee Kwon

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Overexpression of histone deacetylase 6 (HDAC6) and bromodomain-containing protein 4 (BRD4) is related to aggressiveness of head and neck squamous carcinoma (HNSCC). Based on studies that HDAC6 and BRD4 are potential therapeutic targets of HNSCC, we hypothesized that the combination treatment of BET inhibitor JQ1 and HDAC6-selective inhibitor ACY-241 could exhibit synergistic anticancer effects in human papillomavirus (HPV)-positive and HPV-negative HNSCC cells. In this study, HNSCC cell growth and viability were measured by CCK-8 assay, apoptosis was analyzed by flow cytometry, and metastasis was studied by wound healing and transwell assays. Furthermore, immunoblotting is conducted to investigate proteins that modulate apoptosis or metastasis. Here, we report that the combination of ACY-241 and JQ1 shows synergistic cell growth inhibition, viability reduction, and apoptosis induction in HNSCC cells through inactivation of AKT and NF-κB signaling. Importantly, we demonstrate that combined treatment of ACY-241 and JQ1 synergistically suppresses TNF-α-induced migration and invasion via dysregulating matrix metalloproteinase (MMP)-2, MMP-9, and MT1-MMP. Overall, the combination of ACY-241 and JQ1 significantly suppresses proliferation and metastasis in HPV-positive and HPV-negative HNSCC. Collectively, these findings suggest that the co-inhibition of BET and HDAC6 can be a new therapeutic strategy in HNSCC.

Original languageEnglish
Article number6873
Pages (from-to)1-17
Number of pages17
JournalInternational journal of molecular sciences
Volume21
Issue number18
DOIs
Publication statusPublished - 2020 Sep 2

Bibliographical note

Funding Information:
Funding: This research was funded by the Ministry of Education, Science, and Technology (2018R1A6A1A03023718 and 2019R1A2C1008619).

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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