Abstract
Portimine is a bioactive compound produced by the marine algae Vulcanodinium rugosum. It is a member of the cyclic imine family. Cyclic imines are fast-acting toxins that destroy muscular and respiratory systems in animals, by binding to acetylcholine receptors. However, portimine is not lethal to mice, but it does have potent cytotoxicity toward cultured cell lines. It triggers apoptosis, but its mechanism of action is unclear.
Portimine has previously been tested against a panel of 60 cancer cell lines at the US National Cancer Institute. At 3nM, the lowest dose used in the screen, portimine completely inhibited proliferation in the majority of the cell lines. I measured the concentrations of portimine required to slow cell proliferation by 50% (GI50) in the leukaemia Jurkat T-lymphoma and RPMI 8226 cells, MM1R and MM1S myeloma cells, LOX IMVI, M14, and MDA-MB 432 melanoma cultured cancer cell lines. These GI50 values ranged from 0.23 to 1.87 nM. Jurkat T-lymphoma cells overexpressing Bcl-2, which makes them resistant to apoptosis and the cytotoxicity of portimine, had a GI50 of 0.50 nM, indicating that growth arrest occurs independently of the induction of apoptosis.
To investigate how portimine inhibits cell proliferation, I used biotinylated portimine in combination with streptavidin dynabeads to pull out target proteins. Biotinylated portimine had a GI50 of 1.36 nM, in Jurkat T-lymphoma cells, indicating that the biotin tag did not dramatically impact its biological activity. Hundreds of proteins were captured and identified by mass spectrometry, however, a lot of the same proteins appeared in the biotin control. This suggests a more selective pull-down is required to determine the proteins of most interest. This could provide insight into the mechanism of portimine action, and reveal novel therapeutic targets.