Apigenin as a Multi-Targeted Agent in Gastrointestinal Cancers: A Systems Pharmacology Approach

Area of Science:

• Integrative systems pharmacology
• Molecular mechanisms of anticancer agents
• Gastrointestinal oncology

Background:

• Apigenin, a dietary flavonoid, exhibits anticancer properties.
• The multi-targeted molecular mechanisms of apigenin in gastrointestinal (GI) cancers are not well understood.
• Understanding these mechanisms is crucial for developing novel cancer therapies.

Purpose of the Study:

• To comprehensively identify key molecular targets of apigenin in five major GI cancers.
• To elucidate the signaling pathways influenced by apigenin.
• To evaluate the potential of apigenin as a multi-target anticancer agent.

Main Methods:

• Identification of apigenin-related genes from public databases and literature.
• Construction of protein-protein interaction (PPI) networks and hub gene identification.
• Functional enrichment, survival, and gene expression analyses using STRING, DAVID, and GEPIA.
• Molecular docking to assess binding affinities between apigenin and oncogenic proteins.

Main Results:

• Key hub genes including TP53, AKT1, STAT3, BCL2, and HIF1A were identified.
• HIF1A, IL6, and STAT3 were significantly upregulated and associated with poor prognosis.
• Apigenin targets are involved in PI3K-Akt, MAPK, JAK-STAT, and mTOR signaling pathways.
• Molecular docking confirmed high binding affinity of apigenin to AKT1 and PTEN.

Conclusions:

• Apigenin exerts anticancer effects by modulating multiple oncogenic pathways and interacting with key proteins.
• This study provides evidence for apigenin's pleiotropic anticancer potential in GI cancers.
• Apigenin supports development as a multi-target agent in precision oncology.