Differential effect of lonidamine on the plasma membrane ultrastructure of normal and leukemic human lymphocytes

The effect of Lonidamine on the plasma membrane ultrastructure of normal and leukemic human peripheral blood lymphocytes (hPBL) was studied by freeze-fracture electron microscopy. Lonidamine induces remarkable changes in the intramembrane particle distribution on both fracture faces of the plasma membrane as well as of the intracytoplasmic membranes. In particular, a dose-dependent clustering of intramembrane particles was observed in all cell types examined, i.e., normal T and B lymphocytes, T cells from acute lymphoblastic leukemia, and B cells from chronic lymphocytic leukemia, though to a different extent. Normal T lymphocytes appear to be the most sensitive to the action of the drug, while corresponding B cells are much less affected. As regards leukemic cells, in T lymphoblasts the ultrastructural membrane changes are lower than in normal T lymphocytes, whereas leukemic B cells show the same low response to Lonidamine treatment as their normal counterpart. Such a differential effect may be explained by the different membrane molecular organization displayed by normal T and B lymphocytes and by normal and leukemic cells. Moreover, the extent of the ultrastructural modifications at the plasma membrane level, correlates well with literature data on the inhibition of the aerobic glycolysis induced by Lonidamine on the different lymphoid cell types. These findings seem to further confirm that cell membranes are the primary targets of Lonidamine action.