Proteomic level changes associated with S3I201 treated U87 glioma cells.

Glioblastoma multiforme is Grade IV brain tumor associated with high mortality and limited therapeutics. Signal Transducer and Activator of Transcription 3 (STAT3) is persistently active in several cancers including gliomas, and plays a major role in disease progression and survival of glioma patients, thus being a potential therapeutic target for treatment. S3I201 and its analogs inhibit the transcriptional functions of STAT3 and reduce growth of tumor tissues. Here we have studied proteomic alteration associated with S3I201 treated U87 cells using 2-DE and Isobaric tags for relative and absolute quantitation coupled with mass spectrometry. This analysis revealed 136 differentially expressed proteins which were functionally classified with gene ontology analysis. Results showed metabolism, apoptosis, cytoskeletal behaviour, cell redox homeostasis and immune response as the most affected biological processes on S3I201 treatment. Apoptosis-inducing factor 1 mitochondrial, cyclophilin A and chloride intra-cellular channel protein 1 were found to be up-regulated which possibly contributes to its anti-tumorigenic function. Several glycolytic enzymes like phosphoglycerate mutase 1 were also found to be up-regulated and its expression was validated using immunoblot. Conclusively, our study shows the downstream effects of S3I201 in U87 glioma cells and suggests its therapeutic potential.

Pubmed ID: 27565396