3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation.
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| Abstract |
The novel cyclic dinucleotide, 3',5'-cyclic diguanylic acid, cGpGp (c-di-GMP), is a naturally occurring small molecule that regulates important signaling mechanisms in prokaryotes. Recently, we showed that c-di-GMP has "drug-like" properties and that c-di-GMP treatment might be a useful antimicrobial approach to attenuate the virulence and pathogenesis of Staphylococcus aureus and prevent or treat infection. In the present communication, we report that c-di-GMP (50 microM) has striking properties regarding inhibition of cancer cell proliferation in vitro. c-di-GMP inhibits both basal and growth factor (acetylcholine and epidermal growth factor)-induced cell proliferation of human colon cancer (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP at biologically relevant doses showed no lethal cytotoxicity. Cyclic dinucleotides, such as c-di-GMP, represent an attractive and novel "drug-platform technology" that can be used not only to develop new antimicrobial agents, but also to develop novel therapeutic agents to prevent or treat cancer.
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| Authors | David K R Karaolis, Kunrong Cheng, Michael Lipsky, Ahmed Elnabawi, Jennifer Catalano, Mamoru Hyodo, Yoshihiro Hayakawa, Jean-Pierre Raufman |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 329 Issue 1 Pg. 40-5 (Apr 01 2005) ISSN: 0006-291X [Print] United States |
| PMID | 15721270 (Publication Type: Journal Article) |
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