Enhancement of saporin toxicity against U937 cells by Gypsophila saponins.

Saporin, a type I ribosome-inactivating protein (RIP), removes an adenine residue from the 28S ribosomal RNA as part of a process that leads to inhibition of protein synthesis. As a result, saporin has been shown to exert a strong toxicity in the immune system against macrophages. However, studies have shown that macrophage-like U937 cells are fully resistant against low concentrations of unmodified and his-tagged saporin solutions (6 pM) that normally kill macrophages and APC. In the studies reported here, we noted that with these cells, these RIP solutions only became highly cytotoxic when they were used in a combined treatment with Gypsophila saponins. We determined that this cytotoxicity was the result of an induction of apoptosis triggered by the now-internalized saporin molecules that had previously remained outside of these cells. The results here indicate that the Gypsophila saponins induce, in some manner yet to be fully defined, a stimulation of the endocytosis of saporin by these cells.