The lectin Griffonia simplicifolia I-A4 (GS I-A4) specifically recognizes terminal alpha-linked N-acetylgalactosaminyl groups and is cytotoxic to the human colon cancer cell lines LS174t and SW1116.
The lectin GS I-A4 binds to terminal alpha-N-acetylgalactosaminyl (GalNAc) groups (which include the Tn antigen), but not to the closely related tumor-associated epitope, sialylated Tn antigen. The lectin also precipitates asialo OSM, but not its native sialylated form. Lectin histochemistry with human colonic tissues showed that GS I-A4 specifically stained specimens of colon cancer and colonic tissues from individuals with FAP; however, normal colonic tissues from patients without colonic disease were rarely stained with this lectin. Glycoconjugates bound by GS I-A4 were observed on the surface membranes of 2 human colon cancer cell lines, LS174t and SW1116, when fluorescein isothiocyanate (FITC)-conjugated GS I-A4 was used. GS I-A4 was toxic to these 2 human colon cancer cell lines in monolayer culture. A dose-response study conducted using 10-160 micrograms/ml, of GS I-A4 demonstrated significant dose-related toxicity against LS174t and SW1116 cells. At concentrations > 80 micrograms/ml, > 99% of LS174t and > 90% of SW1116 cells were killed. Four mM GalNAc specifically inhibited the cytotoxic effect of GS I-A4 (p < 0.001), whereas 4mM N-acetylglucosamine (GlcNAc) had no effect. Two other lectins that recognize terminal alpha-GalNAc residues, DBA and LBL, were significantly less cytotoxic to the colon cancer cells than GS I-A4. In the light of these findings, we speculate that GS I-A4 may have potential use as a diagnostic agent against colorectal cancer.
Chen
Y F
YF
Department of Biological Chemistry, University of Michigan, Ann Arbor.
Boland
C R
CR
Kraus
E R
ER
Goldstein
I J
IJ
D000116:Acetylgalactosamine / Q000378:metabolism*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D000939:Epitopes / Q000378:metabolism; D006001:Glycoconjugates / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism* / Q000633:toxicity*; D037121:Plant Lectins; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D015295:Antigens, Tumor-Associated, Carbohydrate; D000939:Epitopes; D006001:Glycoconjugates; C045475:Griffonia simplicifolia lectins; D037102:Lectins; D037121:Plant Lectins; C040286:Tn antigen; C036554:dolichos biflorus agglutinin; C031887:lima bean lectin; C055491:sialosyl-Tn antigen; D000116:Acetylgalactosamine