Opposite effects on human colon cancer cell proliferation of two dietary Thomsen-Friedenreich antigen-binding lectins

Increased cell surface expression of the Thomsen-Friedenreich antigen (TF a ntigen, Gal beta1-3GalNAc alpha-) is a common feature in malignant and pre- malignant epithelia. Our previous studies have shown that dietary TF-bindin g lectins from peanut (Arachis hypogea) and edible mushroom (Agaricus bispo rus) produce marked but different effects on human intestinal epithelial ce ll proliferation. This study investigates the proliferative effects of the other two known dietary TF-binding lectins: jacalin (Artocarpus integrifoli a, JAC) and amaranth lectin (Amaranthus caudatus, ACA). JAC produced dose-d ependent and non-cytotoxic inhibition of proliferation in HT29 human colon cancer cells with maximal effects of 46 +/- 4% at 20 mug/ml, whereas ACA pr oduced dose-dependent stimulation of proliferation with maximal effects of 22 +/- 13% at 20 mug/ml when assessed both by incorporation of [H-3]thymidi ne into DNA and by cell counting. The lectin-mediated effects were inhibita ble by the presence of appropriate Gal beta1-3GalNAc-expressing glycoprotei ns but differences existed between IAC and ACA in their patterns of inhibit ion by such substances. Ligand binding equilibrium studies using iodinated lectins revealed different Kd of the two lectins for HT29 cell surface glyc oproteins. Lectin blots of cell membrane extracts showed different binding patterns in all the four TF-binding lectins. These results provide further evidence that dietary TF-binding lectins can have marked effects on the pro liferation of human malignant gastro-intestinal epithelial cells and hence may play a role in intestinal cancer development, and also show that the bi ological effects of dietary lectins cannot be predicted solely from their c arbohydrate binding properties. J. Cell. Physiol. 186:282-287, 2001. (C) 20 01 Wiley-Liss, Inc.