title: 3',5'-Cyclic diguanylic acid (c-di-GMP) inhibits basal and growth factor-stimulated human colon cancer cell proliferation.
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.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. karaolis@umaryland.edu
authors.forename: David K R
authors.initials: DK
authors.lastname: Karaolis
authors.forename: Kunrong
authors.initials: K
authors.lastname: Cheng
authors.forename: Michael
authors.initials: M
authors.lastname: Lipsky
authors.forename: Ahmed
authors.initials: A
authors.lastname: Elnabawi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Catalano
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Raufman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008958:Models, Molecular; D009447:Neuroblastoma / Q000473:pathology; D051381:Rats; D013211:Staphylococcus aureus / Q000378:metabolism
chemical_list: D006133:Growth Substances; C062025:bis(3',5')-cyclic diguanylic acid; D004815:Epidermal Growth Factor; D006152:Cyclic GMP; D000109:Acetylcholine