myriaporone-3 and Neoplasms

Myriaporone 3/4, a cytotoxic polyketide, has been reported as an inhibitor of eukaryotic protein synthesis. However, the mechanism by which it inhibits translation was unknown. Here we show that myriaporone 3/4 stalls protein synthesis in the elongation phase by inducing phosphorylation of eukaryotic elongation factor 2. The phosphorylation results from direct binding of myriaporone 3/4 to eukaryotic elongation factor 2 kinase. Our study also shows that myriaporone 3/4 in the nanomolar range inhibits in vitro tube formation by endothelial cells without being cytotoxic. In general, myriaporone 3/4 was at least 300 times less toxic to primary cells than to tumor cells.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Bryozoa; Cell Line; Cell Line, Tumor; Cell Proliferation; Elongation Factor 2 Kinase; Epoxy Compounds; Humans; Neoplasms; Peptide Elongation Factor 2; Phosphorylation; Protein Biosynthesis; Pyrans