2. Academic Validation
  3. Dendrobin A inhibits gastric cancer: Mechanistic insights supported by integrated evidence

Dendrobin A inhibits gastric cancer: Mechanistic insights supported by integrated evidence

  • Phytomedicine. 2025 Nov:147:157215. doi: 10.1016/j.phymed.2025.157215.
Yonghao Fan 1,  Yan Chen 2,  Wenyan Lu 2,  Kaijia Shi 2,  Yangyang Zhao 2,  Cheng Zhang 2,  Zhihua Shen 3,  Shaojiang Zheng 4,  Wei Jie 5
Affiliations

Affiliations

  • 1 Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou 571199, China; Department of General Medicine, West China Lecheng Hospital of Sichuan University, Boao 571400, China.
  • 2 Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou 571199, China.
  • 3 Department of Pathophysiology, School of Basic Medicine Sciences, Guangdong Medical University, Zhanjiang 524023, China. Electronic address: shenzh@gdmu.edu.cn.
  • 4 Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou 571199, China. Electronic address: zshaojiang@muhn.edu.cn.
  • 5 Key Laboratory of Emergency and Trauma of Ministry of Education, Engineering Research Center for Hainan Biological Sample Resources of Major Diseases, the Hainan Branch of National Clinical Research Center for Cancer, the First Affiliated Hospital, Hainan Medical University, Haikou 571199, China; Key Laboratory of Tropical Translational Medicine of Ministry of Education, School of Public Health, Hainan Medical University, Haikou 571199, China. Electronic address: wei_jie@muhn.edu.cn.
PMID: 40913985 DOI: 10.1016/j.phymed.2025.157215
Abstract

Background: Traditional Chinese medicine (TCM) has shown anti-tumor potential, but its molecular mechanisms remain poorly understood. This integrated bioinformatics, network pharmacology, and experimental study investigated the anti-cancer effects and mechanisms of Dendrobin A, a pharmacologically active bibenzyl compound from Dendrobium nobile, in gastric Cancer (GC).

Methods: Differentially expressed genes (DEGs) were identified through analysis of the TCGA-STAD dataset. Weighted Gene Co-Expression Network Analysis (WGCNA) highlighted genes related to gastric malignancy. Dendrobin A targets were predicted using SwissTargetPrediction, PharmMapper, and SuperPred. Key pathways were revealed through machine learning and enrichment analysis. Molecular docking, dynamics simulations, and cellular protein thermal stability assays assessed the binding stability between Dendrobin A and core targets. In vitro, Dendrobin A's effects on GC Cell Biology were evaluated. The antitumor activity was evaluated in mouse xenograft model.

Results: Among 3367 DEGs, 454 predicted Dendrobin A targets intersected, with 23 genes enriched in P53 and PI3K-Akt pathways. HSP90AB1, CDK2, and PARP1 were identified as core targets interacting with Dendrobin A. Dendrobin A significantly inhibited proliferation, induced S-phase arrest, promoted Apoptosis, and modulated P53 and PI3K-Akt signaling in GC cells. Application of the P53 inhibitor Pifithrin-α and PI3K agonist Recilisib restored the effects of Dendrobin A on the proliferation and migration of GC cells. In vivo, Dendrobin A reduced tumor growth, downregulated HSP90AB1, CDK2, PARP1, p-PI3K, and p-Akt, and upregulated P53 and P21.

Conclusion: Dendrobin A exerts potent anti-GC effects by inhibiting HSP90AB1/CDK2/PARP1 expression and modulating P53/PI3K-Akt signaling, supporting its therapeutic potential.

Keywords

Dendrobin A; Gastric cancer; Molecular docking; Network pharmacology; P53 signaling; PI3K–Akt pathway; WGCNA.

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