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Schisandrin B targets CD44 to inhibit glioblastoma multiforme
Na Wang1, Yuxin Xie2, Jialin Chen2
1Department of Neurology, The First People's Hospital of Shangqiu, Shangqiu, 476100, China.
Abstract:
Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, responds poorly to surgery, radiotherapy, chemotherapy, and immunotherapy, with dismal prognosis and short median survival. There is an urgent need for improved therapies, with supportive and palliative care integral to the multimodal treatment strategy. Traditional Chinese medicine (TCM) exerts antitumor effects via multi-target and multi-pathway mechanisms. Thus, screening and validation of candidate natural small molecules for the therapy and adjuvant therapy of glioblastoma multiforme (GBM) are of great significance. In this study, bioinformatics analysis identified cluster of differentiation 44 (CD44) as a positive correlate of glioblastoma multiforme (GBM). Using cluster of differentiation 44 (CD44) protein structure from the AlphaFold Protein Structure Database, we combined network pharmacology, virtual screening, and molecular docking to pinpoint Schisandrin B (Sch B) as a candidate natural small molecule against glioblastoma multiforme (GBM). In vitro assays verified that Schisandrin B (Sch B) potently inhibited glioblastoma multiforme (GBM) cell proliferation, migration, and invasion. In vivo glioblastoma multiforme (GBM) xenograft models confirmed that Schisandrin B (Sch B) reduced tumor volume, improved mouse survival, and enhanced autonomous activity. Safety evaluations further demonstrated that Schisandrin B (Sch B) had no adverse effects on mouse body weight, autonomous activity, organ index, or tissue morphology. Taken together, Schisandrin B (Sch B) targets cluster of differentiation 44 (CD44) to inhibit glioblastoma multiforme (GBM), and it has relatively good safety performance. This study can provide a research foundation for the therapy and adjuvant therapy of glioblastoma multiforme (GBM).
Insights
Schisandrin B effectively targets cluster of differentiation 44 (CD44) to inhibit glioblastoma multiforme (GBM) growth and spread. This natural compound shows promise as a safe and effective therapy or adjuvant for glioblastoma multiforme (GBM).
Area of Science:
- Oncology
- Pharmacology
- Bioinformatics
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor treatment outcomes.
- There is a critical need for novel therapeutic strategies, including natural compounds, to combat GBM.
- Traditional Chinese Medicine (TCM) offers potential multi-target approaches for cancer therapy.
Purpose of the Study:
- To identify and validate natural small molecules as potential glioblastoma multiforme (GBM) therapeutics.
- To investigate the efficacy and safety of Schisandrin B (Sch B) as an anti-GBM agent.
- To explore the molecular mechanisms underlying Schisandrin B's (Sch B) anti-tumor activity.
Main Methods:
- Bioinformatics analysis to identify potential GBM targets, specifically cluster of differentiation 44 (CD44).
- Network pharmacology, virtual screening, and molecular docking to identify Schisandrin B (Sch B) as a candidate.
- In vitro cell-based assays and in vivo xenograft models to evaluate efficacy and safety.
Main Results:
- Cluster of differentiation 44 (CD44) was identified as a key correlate of glioblastoma multiforme (GBM).
- Schisandrin B (Sch B) significantly inhibited GBM cell proliferation, migration, and invasion in vitro.
- Schisandrin B (Sch B) reduced tumor volume, improved survival, and enhanced activity in vivo with no observed adverse effects.
Conclusions:
- Schisandrin B (Sch B) demonstrates potent anti-GBM activity by targeting cluster of differentiation 44 (CD44).
- Schisandrin B (Sch B) exhibits a favorable safety profile, making it a promising candidate for glioblastoma multiforme (GBM) therapy.
- This study provides a strong foundation for developing Schisandrin B (Sch B) as a therapeutic or adjuvant treatment for glioblastoma multiforme (GBM).
