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 β-catenin and disrupted the Wnt/β-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
β-catenin, and disrupting the Wnt/β-catenin pathway, in turn reducing the expression of PD-L1 and improving
Jurkat cell immunity.