Inhibitory effects of phytohemagglutinin isolectins L4 and E4 on L1210 cells

Phytohemagglutinin isolectins L4 and E4 inhibit the growth and proliferation of cultured L1210 murine leukemia cells. L1210 cells were incubated with L4 or E4, and the metabolic and morphological characteristics of the cells were assessed. Dose-dependent inhibition of up to 90% occurs for [3H]thymidine and [14C]uridine incorporation. L4 is 30 to 50 times more potent an inhibitor than is E4. Inhibition begins 2 to 3 hr after exposure of L1210 cells to L4 and persists for as long as the cells are exposed to this isoleuctin. Total DNA and oxygen consumption in L4-treated cultures is also decreased. Whereas protein synthesis assessed by [14C]valine incorporation is less affected, glucose utilization remains unchanged. The binding of L4 and E4 to L1210 cells and human lymphocytes is similar and is reversible by porcine thyroglobulin. Porcine thyroglobulin also reverses L4-induced inhibition of nucleotide incorporation. Cell aggregation is the major morphological consequence of isoleuctin treatment observed by light or electron microscopy. L1210 cells are agglutinated at lower doses of isoleuctins than are normal murine lymphocytes. No evidence of cell death as estimated by 51Cr release or trypan blue uptake has been noted. Our data indicate that L4 and E4 have cytostatic properties and demonstrate that the reversible binding of a macromolecule to the surface of a malignant cell can modulate synthetic pathways and the rate of proliferation.