Related Experiment Video
Updated: Aug 23, 2026
Establishment and Histological Analysis of Esophageal Organoids Modeling the Progression from Normal to Cancerous Tissues
Published on: May 30, 2025
Network pharmacology-guided identification and validation of ganoderic acids A and D from Ganoderma lucidum against
Yu Wang1, Yinchun Xie2, Shishi Meng3
1School of Pharmaceutical Sciences, Shenzhen University Medical School, Shenzhen, Guangdong, 518055, China; School of Pharmacy, Jinan University, Guangzhou, Guangdong, 510630, China.
Background/Objective:
Esophageal squamous cell carcinoma (ESCC) is a highly aggressive malignancy with unsatisfactory prognosis and ongoing therapeutic challenges. Ganoderma lucidum has been widely investigated for anticancer activity, but the specific monomeric ganoderic acids that may contribute to anti-ESCC effects and their potential target context remain insufficiently characterized.
Methods:
Compounds and targets were prioritized through network pharmacology, ADME evaluation, disease-target integration and TCGA-based clinical bioinformatics. Molecular docking and 100-ns molecular dynamics (MD) simulations were used to evaluate putative ligand-target binding stability. The effects of ganoderic acid A (GA-A) and ganoderic acid D (GA-D) were assessed in ESCC and normal esophageal epithelial cells using image-based cell counting, EdU incorporation assays, flow cytometric cell-cycle and apoptosis analyses, and immunoblotting of mTORC1-associated readouts.
Results:
Nine compounds and 191 drug-disease intersection targets were identified. GA-A and GA-D were prioritized as core ganoderic acid monomers based on network connectivity, pharmacological relevance and experimental feasibility. Enrichment analysis implicated cancer-related signaling, including PI3K-Akt/mTOR-associated pathways. Docking and MD simulations supported stable putative interactions between GA-A/GA-D and mTOR. In vitro, both compounds reduced cell number and EdU incorporation in ECSS cells, and induced G0/G1 accumulation and apoptosis, with GA-D showing stronger anti-proliferative activity than GA-A under the tested conditions. HEEC cells were less sensitive under the tested conditions. GA-A and GA-D also reduced phosphorylated S6 and 4EBP1 levels.
Conclusion:
This study identifies GA-A and GA-D, particularly GA-D, as candidate anti-proliferative monomers from G. lucidum against ESCC. The findings provide a focused, experimentally supported basis for further mechanistic evaluation of ganoderic acids, including target engagement assays and drug-treated transcriptomic profiling.
Insights
Ganoderma lucidum monomers, ganoderic acid A (GA-A) and ganoderic acid D (GA-D), show anti-proliferative effects against esophageal squamous cell carcinoma (ESCC). GA-D demonstrates stronger activity, targeting the mTOR pathway for potential cancer therapy.
Area of Science:
- Integrative oncology
- Network pharmacology
- Molecular biology
Background:
- Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with poor outcomes.
- Ganoderma lucidum exhibits anticancer properties, but specific active compounds against ESCC are not well-defined.
- Identifying effective monomers and their molecular targets is crucial for ESCC treatment development.
Purpose of the Study:
- To identify specific monomeric ganoderic acids from Ganoderma lucidum with anti-ESCC activity.
- To elucidate the molecular targets and pathways involved in the anti-ESCC effects of these compounds.
- To evaluate the therapeutic potential of ganoderic acid A (GA-A) and ganoderic acid D (GA-D) against ESCC.
Main Methods:
- Network pharmacology and bioinformatics analyses prioritized GA-A and GA-D.
- Molecular docking and dynamics simulations assessed ligand-target interactions, focusing on mTOR.
- In vitro assays evaluated GA-A and GA-D effects on ESCC cell proliferation, cell cycle, apoptosis, and key signaling proteins.
Main Results:
- GA-A and GA-D were identified as key ganoderic acid monomers with potential anti-ESCC activity.
- Molecular simulations predicted stable binding of GA-A and GA-D to mTOR.
- In vitro, both compounds inhibited ESCC cell proliferation and induced apoptosis, with GA-D showing superior efficacy; they also reduced mTORC1 signaling.
Conclusions:
- GA-A and GA-D, particularly GA-D, are promising anti-proliferative agents against ESCC.
- These findings support further investigation into ganoderic acids as targeted therapies for ESCC.
- Future studies should include mechanistic evaluations and transcriptomic profiling of drug-treated cells.