Early Events in the Selective Cytotoxicity to Tumor Cells Induced by Liposomes Containing Plant Phosphatidylinositol

Summary

Recently we reported a cytotoxic effect induced by liposomes comprised of plant phosphatidylinositol (PI) against 10 out of 11 cultured tumor cell lines but not against 4 normal cell lines. The cytotoxicity was not observed with liposomes comprised of other negatively charged phospholipids, including animal PI. Cytotoxicity against tumor cells was most obvious 72 h after incubation of the cells with plant PI liposomes. In this paper, we describe an early biochemical event that occurs prior to the onset of overt cytotoxicity. We have documented a dramatic drop in uptake of inositol that occurs as early as 3 h after incubation of the cells with plant PI liposomes. The decrease in inositol uptake is not seen with normal cells, nor does it occur in tumor cells exposed to liposomes comprised of animal PI. Therefore, we conclude that interference with PI turnover may be an important early event in the development of cytotoxicity against tumor cells.