Hyperoside Inhibits RNF8-mediated Nuclear Translocation of ß-catenin to Repress PD-L1 Expression and Prostate Cancer.
Anticancer Agents Med Chem
; 24(6): 464-476, 2024.
Article
en En
| MEDLINE
| ID: mdl-38305391
ABSTRACT
BACKGROUND:
Hyperoside is a flavonol glycoside isolated from Hypericum perforatum L. that has inhibitory effects on cancer cells; however, its effects on prostate cancer (PCa) remain unclear. Therefore, we studied the anti-PCa effects of hyperoside and its underlying mechanisms in vitro and in vivo.AIM:
This study aimed to explore the mechanism of hyperoside in anti-PCa.METHODS:
3-(4,5-Dimethyl-2-Thiazolyl)-2,5-Diphenyl Tetrazolium Bromide (MTT), transwell, and flow cytometry assays were used to detect PCa cell growth, invasion, and cell apoptosis. Immunoblot analysis, immunofluorescence, immunoprecipitation, and quantitative real-time PCR (qRT-PCR) were used to analyze the antitumor mechanism of hyperoside.RESULTS:
Hyperoside inhibited PCa cell growth, invasion, and cell cycle and induced cell apoptosis. Furthermore, RING finger protein 8 (RNF8), an E3 ligase that assembles K63 polyubiquitination chains, was predicted to be a direct target of hyperoside and was downregulated by hyperoside. Downregulation of RNF8 by hyperoside impeded the nuclear translocation of ß-catenin and disrupted the Wnt/ß-catenin pathway, which reduced the expression of the target genes c-myc, cyclin D1, and programmed death ligand 1 (PD-L1). Decreased PD-L1 levels contributed to induced immunity in Jurkat cells in vitro. Finally, in vivo studies demonstrated that hyperoside significantly reduced tumor size, inhibited PD-L1 and RNF8 expression, and induced apoptosis in tumor tissues of a subcutaneous mouse model.CONCLUSION:
Hyperoside exerts its anti-PCa effect by reducing RNF8 protein, inhibiting nuclear translocation of ß-catenin, and disrupting the Wnt/ß-catenin pathway, in turn reducing the expression of PD-L1 and improving Jurkat cell immunity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
/
Quercetina
/
Proliferación Celular
/
Beta Catenina
/
Antígeno B7-H1
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Anticancer Agents Med Chem
Asunto de la revista:
ANTINEOPLASICOS
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Países Bajos