Monensin and tunicamycin-induced inhibition of HT29 cell spreading and growth.
HT29 cells originating from a human colon adenocarcinoma, spread very rapidly after seeding on their own extracellular matrix (ECM). Preincubation of cells with the inhibitor of protein glycosylation tunicamycin (TM) or with the ionophore monensin substantially suppressed cell spreading in serum-free medium without affecting cell adhesion to ECM. Addition of the drugs after cell attachment and spreading inhibited cell growth. TM-treated cells remained viable after 6 days of exposure to 2 micrograms ml-1 of TM and resumed their normal growth rate and shape after removing the drug from the medium. On the contrary, monensin inhibition of cell growth was not reversible: after 3 days, cells detached from the ECM and were unable to exclude Trypan Blue. At the ultrastructural level, a swollen Golgi apparatus with numerous vacuoles was observed after treatment for 2 h in either TM or monensin-preincubated cells. These results suggest that TM and monensin interfere with the insertion and, or, function of one or more cell surface glycoproteins, possibly interacting with cytoskeleton and involved in cell spreading and growth.
D000230:Adenocarcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003110:Colonic Neoplasms / Q000473:pathology*; D005663:Furans / Q000494:pharmacology*; D005944:Glucosamine / Q000031:analogs & derivatives*; D006801:Humans; D008854:Microscopy, Electron; D008985:Monensin / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology*
D005663:Furans; D014415:Tunicamycin; D008985:Monensin; D005944:Glucosamine