Proteomic Characterisation of Pateamine A Treatment of Glioblastoma

Pateamine A is a potent inhibitor of eukaryotic translation initiation factor eIF4A, with potential application in cancer treatment. Glioblastoma is a highly aggressive and clinically challenging type of brain cancer. Existing evidence shows glioblastoma exhibit an abnormal energy metabolism, and there is also evidence that pateamine A causes alterations in the energy metabolism of other cancer cell lines. This research investigates the effects of eIF4A inhibition on biological pathways in glioblastoma cells, via pro- teomic analysis and gene ontology analysis. Characterising changes in the proteome as a result of pateamine inhibition of eIF4A contributes to the understanding of pre-initiation influences on mRNA processing, and elucidates alterations in glioblastoma metabolism following pateamine A treatment.

An elongation inhibitor, cycloheximide, was used as a control, as was a human leukaemia cell line. The two glioblastoma cell lines, LN18 and U87, exhibited direct effects on translation ontologies as a result of cyclohex- imide treatment. When compared to translational inhibition, pateamine A treatment caused alterations in RNA transcription splicing in glioblastoma. Other effects were also seen in ribosomal biogenesis and mitochondrial translation. This research characterised proteomic effects of pateamine A and cycloheximide treatment on two glioblastoma cell lines, and evidenced alterations in a range of cell processes.