Antiproliferative response of human leukemic cells: lectin induced inhibition of DNA synthesis and cellular metabolism.

Proliferation and DNA synthesis of human acute (CCRF-CEM, MOLT-4, JM, T-45) and chronic (SKW-3) lymphocytic leukemia cell lines of T-cell type were inhibited in a dose dependent fashion by the isolectins of phytohemagglutinin (PHA). PHA isolectin with four L subunits (PHA-L4) induced a significant antiproliferative response of CCRF-CEM and MOLT-4 tumor cells at a concentration of only 0.05 micrograms/ml. A 50% inhibition of DNA synthesis of these two cell lines was obtained at 0.4 and 0.5 micrograms PHA-L4/ml, respectively. The effect was cytostatic rather than cytotoxic. Considerably higher (greater than 10) concentrations of PHA isolectin with four E subunits were needed to induce similar growth inhibition of the tumor cells, as compared to PHA-L4. The effect of PHA isolectins on cellular metabolism of the leukemic cell lines was measured using microcalorimetry. The rate of heat production (thermal power), which is the net effect of all metabolic pathways, was decreased already after a 30-min culture of tumor cells in the presence of isolectin. PHA-L4 showed a significant inhibitory effect at a concentration of 0.1 micrograms/ml, whereas approximately 200 times more of PHA isolectin with four E subunits was needed to obtain the same metabolic inhibition. Measurements of glycolytic lactate and oxygen consumption during isolectin treatments supported the fact that the PHA-L4 induced antiproliferative response of human leukemic cell lines was specific and energy dependent. Six and three membrane components involved in the antiproliferative response of CCRF-CEM (ALL) and SKW-3 (CLL) cells, respectively, were isolated by affinity chromatography and characterized by electrophoresis.