Deciphering the Anticancer Effects of Baicalein in Human Gastric Cancer Cells: Computational Chemistry, Bioinformatics, Network Pharmacology Insights, and in vitro Experimental Validation
| Author | Bai Jing | en |
| Author | Ren Hui | en |
| Author | Li Xiao | en |
| Issued Date | 2026-12-31 | en |
| Abstract | Background: Baicalein, a natural flavone, exhibits multifaceted anticancer potential; however, its molecular mechanisms in gastric carcinoma remain unclear. Objectives: This study aimed to elucidate the molecular mechanisms of baicalein in human gastric cancer (GC) using an integrated approach combining computational chemistry, network pharmacology, bioinformatics, and in vitro assays. Methods: Network pharmacology and bioinformatics analyses were conducted to identify hub targets and enriched signaling pathways of baicalein in GC. Molecular docking was then performed to evaluate binding affinities for key proteins, including AKT1, STAT3, and mutant TP53. These in silico findings informed subsequent in vitro validation. The primary outcome was cell viability, assessed by the MTT assay; secondary outcomes included apoptosis, assessed by flow cytometry, and changes in protein expression, assessed by Western blotting. Results: Density functional theory (DFT) analysis indicated favorable electronic properties of baicalein, with a HOMO-LUMO gap of 3.787 eV, and demonstrated similarity to reference inhibitors targeting mutant TP53, AKT, and STAT3. SwissADME indicated drug-likeness, with no rule violations, a bioavailability of 0.55, high gastrointestinal absorption, and blood-brain barrier permeability. Network pharmacology identified 382 targets. Overlap with 1,001 GC genes yielded 181 common targets, forming a significant protein-protein interaction network with 181 nodes and 641 edges and identifying TP53, AKT1, and STAT3 as hubs. The analysis suggested that baicalein may act as a multitarget modulator affecting the PI3K-Akt, MAPK, and apoptosis pathways. In vitro validation supported these predictions. The MTT assay showed selective, dose-dependent cytotoxicity, with IC50 values of 40.25 μM in SGC-7901 cells and 77.95 μM in GES-1 cells. Microscopy confirmed apoptotic morphology, flow cytometry showed increased Annexin V-positive cells consistent with intrinsic apoptosis, and Western blotting revealed downregulation of AKT1 and STAT3 with slight upregulation of mutant TP53, supporting their roles in carcinogenesis. Conclusions: Baicalein may exert selective anticancer effects in GC through multitarget modulation of the PI3K-Akt, MAPK, and apoptosis pathways, particularly via AKT1, STAT3, and mutant TP53. These findings support its potential as a therapeutic candidate, pending further validation. | en |
| DOI | https://doi.org/10.5812/ijpr-171172 | en |
| URI | https://brieflands.com/journals/ijpr/articles/171172 | en |
| Keyword | Baicalein | en |
| Keyword | Network Pharmacology | en |
| Keyword | Computational Chemistry | en |
| Keyword | Apoptosis | en |
| Keyword | Bioinformatics | en |
| Publisher | Brieflands | en |
| Title | Deciphering the Anticancer Effects of Baicalein in Human Gastric Cancer Cells: Computational Chemistry, Bioinformatics, Network Pharmacology Insights, and in vitro Experimental Validation | en |
| Type | Research Article | en |