Exisulind and guanylyl cyclase C induce distinct antineoplastic signaling mechanisms in human colon cancer cells

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Exisulind and guanylyl cyclase C induce distinct antineoplastic signaling mechanisms in human colon cancer cells.

The nonsteroidal anti-inflammatory drug sulindac is metabolized to sulindac sulfone (exisulind), an antineoplastic agent that inhibits growth and induces apoptosis in solid tumors. In colon cancer cells, the antineoplastic effects of exisulind have been attributed, in part, to induction of cyclic guanosine 3',5'-monophosphate (cGMP) signaling through inhibition of cGMP-specific phosphodiesteras...

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Colorectal cancer (CRC) is a major cause of cancer-related mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C (...

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Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma cells.

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, ass...

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Glycosylation of human receptor guanylyl cyclase C

Background Post translational modifications regulate several signalling pathways and glycosylation is emerging as a key player in this regulatory process. Glycosylation of cell surface receptors modulate the downstream signalling pathway and when altered causes a change in the normal physiology of the cell [1]. Guanylyl cyclase C (GC-C) belongs to a group of membrane bound receptors that produc...

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Signaling via guanylyl cyclase C: cGMP, Src and p21

Background Guanylyl cyclase C (GC-C) is a receptor expressed in intestinal epithelial cells and activation of GCC by its ligands elevates intracellular cGMP which results in an inhibition of cell proliferation [1]. Multiple regulatory mechanisms operate in GC-C to modulate its activity, and include ligand binding to the extracellular domain, ATP binding to the kinase homology domain and additio...

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ژورنال

عنوان ژورنال: Molecular Cancer Therapeutics

سال: 2006

ISSN: 1535-7163,1538-8514

DOI: 10.1158/1535-7163.mct-05-0415