Neddylation inhibitor MLN4924 sensitizes head and neck squamous carcinoma cells to (S)-10-hydroxycamptothecin.
Eur J Med Res
; 28(1): 326, 2023 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-37689760
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Camptotecina
/
Neoplasias de Cabeça e Pescoço
Limite:
Humans
Idioma:
En
Revista:
Eur J Med Res
Assunto da revista:
MEDICINA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China