Promotion of differentiation in human colon carcinoma cells by vasoactive intestinal polypeptide.
The effects of vasoactive intestinal polypeptide (VIP) and dibutyryl cyclic adenosine 3':5'monophosphate (dbcAMP) on two human colon carcinoma cell lines, HCT 116 and GEO, were investigated. VIP and dbcAMP inhibited the growth of both cell lines in monolayer culture in a dose-dependent manner. Within 6 h of treatment with 1 mM dbcAMP or 0.3 microM VIP, numerous mucin-like droplets were secreted by GEO cells. VIP and dbcAMP also increased carcinoembryonic antigen (CEA) secretion. In both cell lines, a 9-fold increase in conditioned medium CEA levels was observed at 1 mM dbcAMP and a 2.6-fold increase at 1.5 microM VIP. Time- and concentration-dependent evaluation in cAMP levels were elicited by VIP in the two cell lines. Immunocytochemical studies for cell-surface glycoprotein detection in GEO cells showed that VIP induced a morphological and functional organization of mucin-secreting cells. These results indicate that VIP and dbcAMP have antiproliferative and strong differentiation-promoting effects in colon cancer cells. This is the first report of VIP-induced mucin secretion in colon tumor cells.
Hoosein
N M
NM
Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Black
B E
BE
Brattain
D E
DE
Brattain
M G
MG
D002272:Carcinoembryonic Antigen / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D000242:Cyclic AMP / Q000032:analysis; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009077:Mucins / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002272:Carcinoembryonic Antigen; D009077:Mucins; D005576:Colforsin; D003995:Dibutyryl Cyclic GMP; D014660:Vasoactive Intestinal Peptide; D013806:Theophylline; D000242:Cyclic AMP