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Updated: Dec 20, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma
Ana Elizia M Marques1,2, Carlos Henrique V do Nascimento Filho1, Thamara M Marinho Bezerra1,3
1Laboratory of Epithelial Biology, Department of Periodontics and Oral Medicine, Division of Oral Pathology Oral Radiology and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Introduction:
Alterations of the epigenome may influence cancer initiation and progression. At the cellular level, histones are key regulators of chromatin accessibility and gene transcription; thus, the inhibition of histone deacetylase enzymes (HDACs) constitutes an attractive target for therapy. In this study, we investigated the effects of the HDAC inhibitor entinostat on oral squamous cell carcinoma (OSCC).
Materials And Methods:
We tested the effects of entinostat on OSCC cell lines. Cell viability and growth were analyzed using MTT assay. Cell cycle analysis, cell apoptosis, cancer stem cell (CSC) content, and the concentration of reactive oxygen species (ROS) in OSCC tumor cells were assessed using flow cytometry. The expression of histones and cell cycle regulatory proteins was examined by Western blot.
Results:
The administration of entinostat resulted in reduced proliferation of OSCC cells, followed by cell cycle arrest at the G0/G1 phase, as well as substantial tumor apoptosis. We found an increase in ROS production and significant reductions in CSCs. We also found that entinostat caused increased acetylation histone H3 and histone H4, and changes in the expression of cell cycle-associated proteins such as p21.
Conclusion:
This study indicates that entinostat is a potential novel therapeutic agent for OSCC by halting tumor proliferation, inducing cytotoxicity and intracellular ROS, and attacking the CSCs.
Insights
Entinostat, a histone deacetylase inhibitor, effectively reduces oral squamous cell carcinoma (OSCC) proliferation and cancer stem cells (CSCs). It also induces apoptosis and increases reactive oxygen species (ROS) in OSCC tumor cells.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Epigenetic alterations are implicated in cancer development.
- Histone deacetylase (HDAC) inhibitors represent a promising therapeutic strategy.
- Entinostat targets HDACs, offering potential for cancer treatment.
Purpose of the Study:
- To investigate the therapeutic effects of entinostat on oral squamous cell carcinoma (OSCC).
- To evaluate entinostat's impact on OSCC cell viability, cell cycle, apoptosis, cancer stem cell (CSC) content, and reactive oxygen species (ROS) production.
Main Methods:
- MTT assay for cell viability and growth.
- Flow cytometry for cell cycle, apoptosis, CSC content, and ROS analysis.
- Western blot for histone and cell cycle protein expression.
Main Results:
- Entinostat significantly reduced OSCC cell proliferation and induced G0/G1 cell cycle arrest.
- Increased tumor apoptosis, reactive oxygen species (ROS) production, and decreased cancer stem cell (CSC) populations were observed.
- Entinostat led to increased histone H3 and H4 acetylation and altered p21 expression.
Conclusions:
- Entinostat demonstrates potential as a novel therapeutic agent for OSCC.
- Its mechanisms include halting proliferation, inducing cytotoxicity and ROS, and targeting CSCs.
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