We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
ACY-241, a histone deacetylase 6 inhibitor, suppresses the epithelial-mesenchymal transition in lung cancer cells by downregulating hypoxia-inducible factor-1 alpha.
- Authors
Seong-Jun Park; Naeun Lee; Chul-Ho Jeong
- Abstract
Hypoxia-inducible factor-1 alpha (HIF-1a) is a transcription factor activated under hypoxic conditions, and it plays a crucial role in cellular stress regulation. While HIF-1a activity is essential in normal tissues, its presence in the tumor microenvironment represents a significant risk factor as it can induce angiogenesis and confer resistance to anti-cancer drugs, thereby contributing to poor prognoses. Typically, HIF-1a undergoes rapid degradation in normoxic conditions via oxygen-dependent degradation mechanisms. However, certain cancer cells can express HIF-1a even under normoxia. In this study, we observed an inclination toward increased normoxic HIF-1a expression in cancer cell lines exhibiting increased HDAC6 expression, which prompted the hypothesis that HDAC6 may modulate HIF-1a stability in normoxic conditions. To prove this hypothesis, several cancer cells with relatively higher HIF-1a levels under normoxic conditions were treated with ACY-241, a selective HDAC6 inhibitor, and small interfering RNAs for HDAC6 knockdown. Our data revealed a significant reduction in HIF-1a expression upon HDAC6 inhibition. Moreover, the downregulation of HIF-1a under normoxic conditions decreased zinc finger E-box-binding homeobox 1 expression and increased E-cadherin levels in lung cancer H1975 cells, consequently suppressing cell invasion and migration. ACY-241 treatment also demonstrated an inhibitory effect on cell invasion and migration by reducing HIF-1a level. This study confirms that HDAC6 knockdown and ACY-241 treatment effectively decrease HIF-1a expression under normoxia, thereby suppressing the epithelial-mesenchymal transition. These findings highlight the potential of selective HDAC6 inhibition as an innovative therapeutic strategy for lung cancer.
- Subjects
HYPOXIA-inducible factor 1; EPITHELIAL-mesenchymal transition; HISTONE deacetylase inhibitors; CANCER cells; LUNG cancer; SMALL interfering RNA
- Publication
Korean Journal of Physiology & Pharmacology, 2024, Vol 28, Issue 1, p83
- ISSN
1226-4512
- Publication type
Article
- DOI
10.4196/kjpp.2024.28.1.83