Endogenous anti-tumorigenic nitro-fatty acids inhibit the ubiquitin-proteasome system by directly targeting the 26S proteasome.
Cell Chem Biol
; 30(10): 1277-1294.e12, 2023 10 19.
Article
en En
| MEDLINE
| ID: mdl-37473760
ABSTRACT
Nitro-fatty acids (NFAs) are endogenous lipid mediators causing a spectrum of anti-inflammatory effects by covalent modification of key proteins within inflammatory signaling pathways. Recent animal models of solid tumors have helped demonstrate their potential as anti-tumorigenic therapeutics. This study evaluated the anti-tumorigenic effects of NFAs in colon carcinoma cells and other solid and leukemic tumor cell lines. NFAs inhibited the ubiquitin-proteasome system (UPS) by directly targeting the 26S proteasome, leading to polyubiquitination and inhibition of the proteasome activities. UPS suppression induced the unfolded protein response, resulting in tumor cell death. The NFA-mediated effects were substantial, specific, and enduring, representing a unique mode of action for UPS suppression. This study provides mechanistic insights into the biological actions of NFAs as possible endogenous tumor-suppressive factors, indicating that NFAs might be key structures for designing a novel class of direct proteasome inhibitors.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ubiquitina
/
Complejo de la Endopetidasa Proteasomal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Chem Biol
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania