Natural Product Daidzin Inhibits Glioma Development via Suppressing the LRP5-Mediated GSK-3β/c-Myc Signaling Pathway.

in BioFactors (Oxford, England) by Yijing Pan, Shunshun Wang, Guoliang Duan, Jiaqin Wu, Fan Feng, Lin Chen, Anzheng Li, Kang Xu, Chunli Wang, Shibing Fan

TLDR

  • Daidzin (DZN) exhibits strong antitumor effects in glioblastoma cells and in vivo models, with potential molecular mechanisms involving amino acid metabolism and ubiquitin-mediated proteolysis.
  • LRP5 is identified as a prognostic biomarker in glioblastoma, with DZN treatment decreasing LRP5 activity and inhibiting the Wnt signaling pathway.
  • The study highlights the potential of DZN as a natural and non-toxic therapeutic agent for glioblastoma treatment, with its low toxicity and potential to improve patient outcomes.

Abstract

Daidzin (DZN) is a natural flavonoid compound derived from soybeans that has recently been recognized for its potential antitumor properties. In traditional Chinese medicine, soybeans and their extracts are extensively used to prevent and treat various diseases. To evaluate the therapeutic efficacy of DZN on human glioblastoma through in vivo and in vitro experiments, and through multi-omics analyses to elucidate potential molecular mechanisms. Cell viability of LN-229 and U-87MG glioblastoma cells was assessed using the CCK-8 assay. Protein and mRNA levels of proliferation and apoptosis-related genes were analyzed via Western blotting and qPCR. Metabolomics and transcriptomics identified key pathways and targets, which were confirmed by in-cell Western blotting and expression correlation analysis. The in vivo antitumor effects of DZN were evaluated in nude mice with LN-229 tumors. DZN treatment reduced cell viability, migration, and survival in a dose-dependent manner, demonstrating strong antitumor effects in both in vitro and in vivo models. Multi-omics analysis identified amino acid metabolism and ubiquitin-mediated proteolysis as key mechanisms. Bioinformatics highlighted LRP5 as a prognostic biomarker in glioblastoma. DZN decreased LRP5 activity, downregulated p-GSK-3β, and promoted c-Myc degradation, thereby inhibiting the Wnt signaling pathway. In vivo, DZN significantly reduced tumor size and Ki67 expression. These findings highlight LRP5 as a promising therapeutic target, with DZN emerging as a potent LRP5 inhibitor and exhibiting significant antitumor effects in glioblastoma.

Overview

  • Multi-omics analysis, including metabolomics, transcriptomics, and protein analysis, was used to identify key pathways and targets in addition to evaluating the effects of DZN on cell viability, migration, and survival.
  • In vivo antitumor effects of DZN were evaluated in nude mice with LN-229 tumors, with tumor size and Ki67 expression used as endpoints.
  • The findings highlight the potential of DZN as a natural and non-toxic therapeutic agent for glioblastoma treatment.

Comparative Analysis & Findings

  • Multi-omics analysis identified amino acid metabolism and ubiquitin-mediated proteolysis as key mechanisms underlying DZN's antitumor effects.
  • In vivo, DZN significantly reduced tumor size and Ki67 expression, indicating its potential as a therapeutic agent for glioblastoma treatment.
  • The findings suggest that LRP5 is a key target for glioblastoma treatment, with DZN emerging as a potential therapeutic agent.

Implications and Future Directions

  • Future studies should investigate the use of DZN in combination with other therapeutic agents to enhance its antitumor effects.
  • Further studies should investigate the use of LRP5 inhibitors, such as DZN, in glioblastoma treatment.
  • Future studies should integrate multi-omics analysis with in vitro and in vivo experiments to elucidate the potential mechanisms of DZN's antitumor effects.
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