INHIBITION OF CELL-PROLIFERATION BY RANA-CATESBEIANA AND RANA-JAPONICA LECTINS BELONGING TO THE RIBONUCLEASE SUPERFAMILY

Two frog egg lectins [Rana catesbeiana lectin (SBL-C) and Rana japonic a lectin] preferentially agglutinate a large variety of human and anim al turner cells but not blood cells, lymphocytes, or fibroblasts. Thes e lectins belong to the superfamily of pyrimidine base-specific RNases . The two lectins bound to a heparin-Sepharose column and were eluted from the column by an increase of NaCl molarity. Both their tumor cell -agglutinating activity and RNase activity were inhibited by heparin, and also by polyamines, such as spermine. Both lectins inhibited P388 leukemia cell proliferation. The inhibitory activity of SBL-C was bloc ked by addition of heparin. SBL-C inhibited protein synthesis by P388 cells, but RNase A did not. No lectin-induced antiproliferative effect was observed after sialidase treatment of cells. The antiproliferativ e activity of SBL-C was also inhibited by ammonium chloride treatment. These results suggest that internalization of the lectins by lectin r eceptor (sialoglycoconjugate)-mediated endocytosis is followed by cell death due to inhibition of protein synthesis. Administration of SBL-C i.p. delayed time to death in mice receiving i.p. transplants of Sarc oma 180 and Mep II cells.