Back to Search
Start Over
Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin
- Source :
- European Journal of Medical Research, Vol 28, Iss 1, Pp 1-10 (2023)
- Publication Year :
- 2023
- Publisher :
- BMC, 2023.
-
Abstract
- Abstract Head and neck squamous carcinoma (HNSCC) is the seventh most common cancer worldwide. Targeted therapeutic drugs for HNSCC are still being explored. Among them, (S)-10-hydroxycamptothecin (10-HCPT), a specific inhibitor of TOP1, functions by DNA double-strand breaks that can inhibit DNA replication and trigger apoptotic cell death subsequently. Previous studies have reported that MLN4924 exerts potent anti-tumor effects by inhibiting cullin–RING ligases and causing substrate accumulation in a variety of cancers. Here, we show that MLN4924 effectively causes dose-dependent accumulation of topoisomerase I (TOP1) and blocks TOP1 ubiquitination. Importantly, neddylation inhibition with MLN4924 acts synergistically with 10-HCPT to suppress cell growth, migration and apoptosis in HNSCC cells. Mechanistically, transcriptome sequencing shows that the cytotoxic effects of the combination of MLN4924 and 10-HCPT may involve activation of the NFKB1 pathway. Taken together, our results suggest that combined treatment with MLN4924 and 10-HCPT may be an effective strategy in HNSCC.
Details
- Language :
- English
- ISSN :
- 2047783X
- Volume :
- 28
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- European Journal of Medical Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.7d26ad1eec854a3c91287f1bd9c680e8
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s40001-023-01289-y