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Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman Jul 2001

Guanylyl Cyclase C Agonists Regulate Progression Through The Cell Cycle Of Human Colon Carcinoma Cells., Giovanni Mario Pitari, M D Di Guglielmo, J Park, S Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, …


Guanylyl Cyclase C (Gc-C) Inhibits Human Colon Carcinoma Cell Growth, Giovanni Mario Pitari Jan 2001

Guanylyl Cyclase C (Gc-C) Inhibits Human Colon Carcinoma Cell Growth, Giovanni Mario Pitari

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This is the presentation given for the 2001 Presidential Trainee Young Investigator Award, American Society for Clinical Pharmacology and Therapeutics. An abstract of the presentation has been published in Clin. Pharmacol. Ther., 69(2):P62, 2001. The presentation illustrates the role of the intestinal GC-C receptor as a negative regulator of cell proliferation and cell cycle kinetics in colorectal cancer. It suggests that paracrine GC-C hormones guanylin/uroguanylin are physiological inducers of the proliferation-to-differentiation transition along the intestinal crypt-villus axis. Importantly, the bacterial enterotoxin ST, a potent exogenous GC-C agonist, is offered as a potential cytostatic agent for the prevention and treatment of …