Guanylyl cyclase C (GC-C) inhibits human colon carcinoma cell growth

G. M. Pitari, M. Di Guglielmo, J. Park, S. Schulz, S. Waldman

Research output: Contribution to journalArticle

Abstract

Activation of GC-C in intestine by the E. coli heat-stable toxin (STa) or the endogenous ligands, guanylin and uroguanylin (UG), increases intracellular cyclic GMP (cGMP) regulating fluid and electrolyte homeostasis. The effect of STa and UG on cell growth and viability was examined in 3 human colon carcinoma cell lines. Treatment of T84 and Caco2 cultures, which express GC-C, with STa or UG (1 μM; 48 h) reduced (40-60%) the number of cells, protein content, metabolism of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), and [3H] thymidine incorporation. In contrast, incubation with STa or UG was without effect on SW480 cells, which do not express GC-C. STa or UG did not affect the viability of T84, Caco2 or SW480 cells. The cytostatic effect of STa was dose-dependent, reversible, mimicked by 8-bromo cGMP (5 mM) and not blocked by inhibitors of cyclic nucleotide-dependent protein kinases. Thus, STa and UG inhibit proliferation of human colon carcinoma cell lines by binding to GC-C and stimulating the accumulation of cGMP. These observations suggest that GC-C ligands may be novel cytostatic agents for the treatment of patients with metastatic colorectal cancer.

Original languageEnglish (US)
JournalClinical Pharmacology and Therapeutics
Volume69
Issue number2
StatePublished - 2001

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Colon
Carcinoma
Growth
Cyclic GMP
Cytostatic Agents
Ligands
Cell Line
Cyclic Nucleotides
Thymidine
Protein Kinases
Electrolytes
Intestines
enterotoxin receptor
uroguanylin
Colorectal Neoplasms
Cell Survival
Homeostasis
Cell Count
Therapeutics
Proteins

ASJC Scopus subject areas

  • Pharmacology

Cite this

Pitari, G. M., Di Guglielmo, M., Park, J., Schulz, S., & Waldman, S. (2001). Guanylyl cyclase C (GC-C) inhibits human colon carcinoma cell growth. Clinical Pharmacology and Therapeutics, 69(2).

Guanylyl cyclase C (GC-C) inhibits human colon carcinoma cell growth. / Pitari, G. M.; Di Guglielmo, M.; Park, J.; Schulz, S.; Waldman, S.

In: Clinical Pharmacology and Therapeutics, Vol. 69, No. 2, 2001.

Research output: Contribution to journalArticle

Pitari, GM, Di Guglielmo, M, Park, J, Schulz, S & Waldman, S 2001, 'Guanylyl cyclase C (GC-C) inhibits human colon carcinoma cell growth', Clinical Pharmacology and Therapeutics, vol. 69, no. 2.
Pitari, G. M. ; Di Guglielmo, M. ; Park, J. ; Schulz, S. ; Waldman, S. / Guanylyl cyclase C (GC-C) inhibits human colon carcinoma cell growth. In: Clinical Pharmacology and Therapeutics. 2001 ; Vol. 69, No. 2.
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