Enhancement of Cisplatin Efficacy by the Histone Demethylase Inhibitor JIB-04 in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines
- 1Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093 Lublin, Poland
- 2Department of Physiology and Toxicology, The John Paul II Catholic University of Lublin, 20-708 Lublin, Poland
Abstract
Head and neck squamous cell carcinoma (HNSCC) develops resistance to cisplatin. We investigated whether JIB-04, an inhibitor of Jumonji histone demethylases, enhances cisplatin activity in established HNSCC cell lines. Four UT-SCC cell lines originating from primary tumors and matched lymph-node metastases were treated with JIB-04 and cisplatin, alone or combined. Viability was assessed by MTT assay, and drug interactions were evaluated using the Highest Single Agent model. In UT-SCC-24A cells, we assessed BrdU incorporation, LDH release, cell-cycle distribution, and apoptosis. RNA sequencing was performed after 24 h at the same drug concentrations used in functional assays. JIB-04 reduced viability in all HNSCC lines at submicromolar concentrations, with moderate effects in BJ fibroblasts. HSA analysis identified a localized positive interaction in UT-SCC-24A, where the overall HSA score was 4.25, whereas local scores reached approximately 16–18 within a narrow low-dose range. Co-treatment further reduced DNA synthesis and increased S/G2-M accumulation and apoptosis, without significantly increasing LDH release. RNA sequencing revealed JIB-04-associated induction of integrated stress response/ATF4- and DNA damage response-related genes, alongside suppression of proliferation- and cell-cycle-associated genes. The combination retained these transcriptional features. These findings support the further investigation of JIB-04–cisplatin combinations in selected HNSCC cell-line models.
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BibTeX
@article{adamczuk2026enhancement,
title = {{Enhancement of Cisplatin Efficacy by the Histone Demethylase Inhibitor JIB-04 in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines}},
author = {Kamila Adamczuk and Grzegorz Adamczuk and Michał Kiełbus and Matthias Nees and Andrzej Stepulak},
journal = {Cells},
year = {2026},
month = nov,
doi = {10.3390/cells15212023},
url = {https://www.mdpi.com/2073-4409/15/21/2023},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Enhancement of Cisplatin Efficacy by the Histone Demethylase Inhibitor JIB-04 in Head and Neck Squamous Cell Carcinoma (HNSCC) Cell Lines
AU - Kamila Adamczuk
AU - Grzegorz Adamczuk
AU - Michał Kiełbus
AU - Matthias Nees
AU - Andrzej Stepulak
PY - 2026
DA - 2026/11/06
JO - Cells
DO - 10.3390/cells15212023
UR - https://www.mdpi.com/2073-4409/15/21/2023
AB - Head and neck squamous cell carcinoma (HNSCC) develops resistance to cisplatin. We investigated whether JIB-04, an inhibitor of Jumonji histone demethylases, enhances cisplatin activity in established HNSCC cell lines. Four UT-SCC cell lines originating from primary tumors and matched lymph-node metastases were treated with JIB-04 and cisplatin, alone or combined. Viability was assessed by MTT assay, and drug interactions were evaluated using the Highest Single Agent model. In UT-SCC-24A cells, we assessed BrdU incorporation, LDH release, cell-cycle distribution, and apoptosis. RNA sequencing was performed after 24 h at the same drug concentrations used in functional assays. JIB-04 reduced viability in all HNSCC lines at submicromolar concentrations, with moderate effects in BJ fibroblasts. HSA analysis identified a localized positive interaction in UT-SCC-24A, where the overall HSA score was 4.25, whereas local scores reached approximately 16–18 within a narrow low-dose range. Co-treatment further reduced DNA synthesis and increased S/G2-M accumulation and apoptosis, without significantly increasing LDH release. RNA sequencing revealed JIB-04-associated induction of integrated stress response/ATF4- and DNA damage response-related genes, alongside suppression of proliferation- and cell-cycle-associated genes. The combination retained these transcriptional features. These findings support the further investigation of JIB-04–cisplatin combinations in selected HNSCC cell-line models.
SN - 2073-4409
ER -