Potential mechanisms of osthole against bladder cancer cells based on network pharmacology, molecular docking, and
Yunzhong Jiang1, Mengzhao Zhang2, Lu Wang1
1Department of Urology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Background:
Osthole was traditionally used in treatment for various diseases. However, few studies had demonstrated that osthole could suppress bladder cancer cells and its mechanism was unclear. Therefore, we performed a research to explore the potential mechanism for osthole against bladder cancer.
Methods:
Internet web servers SwissTargetPrediction, PharmMapper, SuperPRED, and TargetNet were used to predict the Osthole targets. GeneCards and the OMIM database were used to indicate bladder cancer targets. The intersection of two target gene fragments was used to obtain the key target genes. Protein-protein interaction (PPI) analysis was performed using the Search Tool for the Retrieval of Interacting Genes (STRING) database. Furthermore, we used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to explore the molecular function of target genes. AutoDock software was then used to perform molecular docking of target genes,osthole and co-crystal ligand. Finally, an in vitro experiment was conducted to validate bladder cancer inhibition by osthole.
Results:
Our analysis identified 369 intersection genes for osthole, the top ten target genes included MAPK1, AKT1, SRC, HRAS, HASP90AA1, PIK3R1, PTPN11, MAPK14, CREBBP, and RXRA. The GO and KEGG pathway enrichment results revealed that the PI3K-AKT pathway was closely correlated with osthole against bladder cancer. The osthole had cytotoxic effect on bladder cancer cells according to the cytotoxic assay. Additionally, osthole blocked the bladder cancer epithelial-mesenchymal transition and promoted bladder cancer cell apoptosis by inhibiting the PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways.
Conclusions:
We found that osthole had cytotoxic effect on bladder cancer cells and inhibited invasion, migration, and epithelial-mesenchymal transition by inhibiting PI3K-AKT and JAK/STAT3 pathways in in vitro experiment. Above all, osthole might have potential significance in treatment of bladder cancer.
Subjects:
Bioinformatics, Computational Biology, Molecular Biology.
Insights
Osthole demonstrates cytotoxic effects on bladder cancer cells, inhibiting invasion and migration. This natural compound may hold potential for future bladder cancer treatments by targeting key signaling pathways.
Area of Science:
- Bioinformatics
- Computational Biology
- Molecular Biology
Background:
- Osthole, a traditional remedy, shows potential in suppressing bladder cancer.
- The precise mechanisms by which osthole affects bladder cancer cells remain largely unexplored.
Purpose of the Study:
- To investigate the potential mechanism of osthole in suppressing bladder cancer.
- To identify key molecular targets and pathways affected by osthole in bladder cancer.
Main Methods:
- Utilized bioinformatics tools (SwissTargetPrediction, PharmMapper, etc.) to predict osthole targets.
- Integrated gene databases (GeneCards, OMIM) for bladder cancer targets and performed intersection analysis.
- Conducted protein-protein interaction (PPI) analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses.
- Validated findings through molecular docking and in vitro cytotoxic assays.
Main Results:
- Identified 369 intersection genes, with MAPK1, AKT1, and SRC among the top targets.
- The PI3K-AKT pathway was significantly correlated with osthole's anti-bladder cancer effects.
- Osthole exhibited cytotoxic effects, inhibited epithelial-mesenchymal transition (EMT), and promoted apoptosis in bladder cancer cells.
- Inhibition of PI3K-AKT and Janus kinase/signal transducer and activator of transcription (JAK/STAT3) pathways was observed.
Conclusions:
- Osthole exhibits cytotoxic effects against bladder cancer cells.
- Osthole inhibits bladder cancer cell invasion, migration, and EMT by targeting PI3K-AKT and JAK/STAT3 pathways.
- Osthole shows promise as a potential therapeutic agent for bladder cancer.
