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Karaolis, D.K. et al.

Karaolis, Cheng, Lipsky, Elnabawi, Catalano, Hyodo, Hayakawa, Raufman,

3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation.

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.[1]

References

3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation. Karaolis, D.K., Cheng, K., Lipsky, M., Elnabawi, A., Catalano, J., Hyodo, M., Hayakawa, Y., Raufman, J.P. Biochem. Biophys. Res. Commun. (2005) [Pubmed]

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