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 antigen, Galbeta1-3GalNAcalpha-) is a common feature in malignant and pre-malignant epithelia. Our previous studies have shown that dietary TF-binding lectins from peanut (Arachis hypogea) and edible mushroom (Agaricus bisporus) produce marked but different effects on human intestinal epithelial cell proliferation. This study investigates the proliferative effects of the other two known dietary TF-binding lectins: jacalin (Artocarpus integrifolia, JAC) and amaranth lectin (Amaranthus caudatus, ACA). JAC produced dose-dependent and non-cytotoxic inhibition of proliferation in HT29 human colon cancer cells with maximal effects of 46 +/- 4% at 20 microg/ml, whereas ACA produced dose-dependent stimulation of proliferation with maximal effects of 22 +/- 3% at 20 microg/ml when assessed both by incorporation of [3H]thymidine into DNA and by cell counting. The lectin-mediated effects were inhibitable by the presence of appropriate Galbeta1-3GalNAc-expressing glycoproteins but differences existed between JAC and ACA in their patterns of inhibition by such substances. Ligand binding equilibrium studies using iodinated lectins revealed different Kd of the two lectins for HT29 cell surface glycoproteins. 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 proliferation of human malignant gastro-intestinal epithelial cells and hence may play a role in intestinal cancer development, and also show that the biological effects of dietary lectins cannot be predicted solely from their carbohydrate binding properties.
Yu
L G
LG
Department of Medicine, University of Liverpool, Liverpool L69 3GA, United Kingdom. lgyu@liv.ac.uk
Milton
J D
JD
Fernig
D G
DG
Rhodes
J M
JM
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000502:physiology; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms; D004032:Diet; D004187:Disaccharides / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D037102:Lectins / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000502:physiology; D009005:Monosaccharides / Q000494:pharmacology; D037121:Plant Lectins; D011975:Receptors, Mitogen / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D004187:Disaccharides; D037102:Lectins; D008562:Membrane Glycoproteins; D009005:Monosaccharides; D037121:Plant Lectins; D011975:Receptors, Mitogen; C043696:jacalin; C422071:lectin, Amaranthus caudatus; C016467:Thomsen-Friedenreich antigen