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Hyperoside Inhibits RNF8-mediated Nuclear Translocation of ß-catenin to Repress PD-L1 Expression and Prostate Cancer.
Chen, Jie; Zhao, Yi; Wang, Xiaoli; Zang, Long; Yin, Dengke; Tan, Song.
Afiliación
  • Chen J; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
  • Zhao Y; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
  • Wang X; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
  • Zang L; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
  • Yin D; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
  • Tan S; School of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui, 230012, China.
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.
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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

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