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

被引:85
作者
Karaolis, DKR [1 ]
Cheng, KR
Lipsky, M
Elnabawi, A
Catalano, J
Hyodo, M
Hayakawa, Y
Raufman, JP
机构
[1] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA
[2] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA
[3] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA
[4] Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA
[5] Nagoya Univ, Grad Sch Informat Sci Human Informat, Nagoya, Aichi 4648601, Japan
[6] Nagoya Univ, JST, CREST, Nagoya, Aichi 4648601, Japan
关键词
3; 5 '-cyclic diguanylic acid; cyclic diguanylate; cyclic di-guanosine-monophosphate; cGpGp; colon cancer; acetylcholine; epidermal growth factor; drug; therapy; therapeutic; prevention; treatment;
D O I
10.1016/j.bbrc.2005.01.093
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 cdi-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 (less than or equal to50 muM) 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 cancel- (H508) cells. Toxicity studies revealed that exposure of normal rat kidney cells and human neuroblastoma cells to c-di-GMP Lit 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. (C) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:40 / 45
页数:6
相关论文
共 15 条
  • [1] Identification and characterization of a Vibrio cholerae gene, mbaA, involved in maintenance of biofilm architecture
    Bomchil, N
    Watnick, P
    Kolter, R
    [J]. JOURNAL OF BACTERIOLOGY, 2003, 185 (04) : 1384 - 1390
  • [2] Cheng KR, 2003, CANCER RES, V63, P6744
  • [3] Autolysis and autoaggregation in Pseudomonas aeruginosa colony morphology mutants
    D'Argenio, DA
    Calfee, MW
    Rainey, PB
    Pesci, EC
    [J]. JOURNAL OF BACTERIOLOGY, 2002, 184 (23) : 6481 - 6489
  • [4] A facile synthesis of cyclic bis(3′→5′)diguanylic acid
    Hayakawa, Y
    Nagata, R
    Hirata, A
    Hyodo, M
    Kawai, R
    [J]. TETRAHEDRON, 2003, 59 (34) : 6465 - 6471
  • [5] IDENTIFICATION OF A NOVEL RESPONSE REGULATOR REQUIRED FOR THE SWARMER-TO-STALKED-CELL TRANSITION IN CAULOBACTER-CRESCENTUS
    HECHT, GB
    NEWTON, A
    [J]. JOURNAL OF BACTERIOLOGY, 1995, 177 (21) : 6223 - 6229
  • [6] An improved method for synthesizing cyclic bis(3′-5′)diguanylic acid (c-di-GMP)
    Hyodo, M
    Hayakawa, Y
    [J]. BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN, 2004, 77 (11) : 2089 - 2093
  • [7] HmsT, a protein essential for expression of the haemin storage (Hms+) phenotype of Yersinia pestis
    Jones, HA
    Lillard, JW
    Perry, RD
    [J]. MICROBIOLOGY-SGM, 1999, 145 : 2117 - 2128
  • [8] KARAOLIS DKR, 2005, IN PRESS ANTIMICROB
  • [9] Identification of genes involved in the switch between the smooth and rugose phenotypes of Vibrio cholerae
    Rashid, MH
    Rajanna, C
    All, A
    Karaolis, DKR
    [J]. FEMS MICROBIOLOGY LETTERS, 2003, 227 (01) : 113 - 119
  • [10] AgfD, the checkpoint of multicellular and aggregative behaviour in Salmonella typhimurium regulates at least two independent pathways
    Römling, U
    Rohde, M
    Olsén, A
    Normark, S
    Reinköster, J
    [J]. MOLECULAR MICROBIOLOGY, 2000, 36 (01) : 10 - 23