Sucralfate impedes intestinal epithelial sheet migration in a Caco-2 cell culture model.
Sucralfate, which binds to the matrix of the ulcer bed, is theoretically advantageous for duodenal ulcer therapy, but has not fulfilled its promise clinically. We examined the effects of sucralfate and related compounds in a human intestinal epithelial (Caco-2) cell culture model of restitution on sheet migration across and adhesion to collagen I. Migration was quantitated across a collagen I matrix treated with sucralfate or related compounds and correlated with cell adhesion. Caco-2 motility was significantly and dose-responsively inhibited by sucralfate at therapeutic luminal concentrations. Sucrose octaacetate, the sucralfate backbone, and lactose octaacetate exhibited similar effects while the beta-bonded disaccharide maltose octaacetate had little effect. Sucrose itself slightly stimulated motility. Adhesion effects paralleled motility. Thus, sucralfate may inhibit intestinal epithelial motility by sterically interfering with adhesion to collagen I. A sucralfate analog with a lactose octaacetate backbone might retain growth factor binding without inhibiting enterocyte motility, perhaps improving its clinical efficacy.
Emenaker
N J
NJ
Department of Surgery, Yale University School of Medicine, New Haven, CT 06520-8062, USA.
Datta
S
S
Basson
M D
MD
D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D018938:Caco-2 Cells / Q000166:cytology* / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D016685:Mitomycin / Q000494:pharmacology; D013392:Sucralfate / Q000494:pharmacology*; D013395:Sucrose / Q000031:analogs & derivatives / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
D000897:Anti-Ulcer Agents; D000903:Antibiotics, Antineoplastic; C026879:sucrose octaacetate; D016685:Mitomycin; D013392:Sucralfate; D013395:Sucrose; D003094:Collagen