Activation of the nucleotide oligomerization domain signaling pathway by the non-bacterially derived xanthone drug 5'6-dimethylxanthenone-4-acetic acid (Vadimezan).

The Journal of Biological Chemistry
Guanjun ChengSteven M Albelda

Abstract

The cytosolic nucleotide-binding oligomerization domain 1 (NOD1)/CARD4 and NOD2/CARD15 proteins are members of NOD-like receptors recognizing specific motifs within peptidoglycans of both Gram-negative and Gram-positive bacteria. NOD1 and NOD2 signal via the downstream adaptor serine/threonine kinase RIP2/CARDIAK/RICK to initiate NF-kappaB activation and the release of inflammatory cytokines/chemokines. In this report, we show that 5,6-dimethylxanthenone-4-acetic acid (DMXAA), a cell-permeable, small molecule that has anti-tumor activity, can also activate NOD1 and NOD2. This was demonstrated: 1) by using human embryonic kidney epithelial (HEK) 293 cells transfected with a NF-kappaB reporter plasmid in combination with NOD1 or NOD2 expression plasmids; 2) by inhibiting DMXAA-induced chemokine (CXCL10) mRNA and protein production in the AB12 mesothelioma cell line using a pharmacological inhibitor of RICK kinase, SB20358; and 3) by using small interfering RNA to knock down NOD2 and lentiviral short hairpin RNA to knock down RICK. These findings expand the potential ligands for the NOD-like receptors, suggesting that other xanthone compounds may act similarly and could be developed as anti-tumor agents. This information also expa...Continue Reading

References

Jan 16, 1991·Journal of the National Cancer Institute·K A HavlinD D Von Hoff
Jan 1, 1986·Investigational New Drugs·T H CorbettF Valeriote
Jan 1, 1994·Advances in Pharmacology·I J Fidler
Nov 4, 2000·The Journal of Biological Chemistry·N InoharaG Nuñez
Mar 16, 2002·Nature Structural Biology·Christopher PargellisJohn Regan
Aug 2, 2002·The Journal of Biological Chemistry·Margreet A WolfertJames N Moore
Jan 7, 2003·The Journal of Biological Chemistry·Naohiro InoharaGabriel Nuñez
Jun 7, 2003·Science·Stephen E GirardinDana J Philpott
Jul 23, 2003·The Journal of Biological Chemistry·Stephen E GirardinDominique Mengin-Lecreulx
Dec 12, 2003·Proceedings of the National Academy of Sciences of the United States of America·Klaus GodlHenrik Daub
Jun 25, 2004·The Journal of Biological Chemistry·Bastian OpitzStefan Hippenstiel
Aug 4, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Eike HollenbachMichael Naumann
Mar 10, 2005·The Journal of Biological Chemistry·Yvonne KumaAna Cuenda
Oct 28, 2005·Current Medicinal Chemistry·M M M PintoM S J Nascimento
Feb 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jong-Hwan ParkGabriel Núñez
Feb 17, 2007·The Journal of Biological Chemistry·Ling ZhaoDaniel H Hwang
Mar 14, 2007·The Biochemical Journal·Mark WindheimPhilip Cohen
Mar 30, 2007·The Journal of Biological Chemistry·Andrei E MedvedevStefanie N Vogel
Jun 15, 2007·The Journal of Experimental Medicine·Zachary J RobertsStefanie N Vogel
Dec 15, 2007·The EMBO Journal·Mizuho HasegawaNaohiro Inohara
Feb 1, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paul A MeyersUNKNOWN Children's Oncology Group
Apr 3, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jing LiSharyn D Baker
Oct 22, 2008·Annual Review of Pathology·Grace ChenGabriel Nuñez
May 5, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Mark J McKeageJoachim Von Pawel
Aug 4, 2009·Neoplasia : an International Journal for Oncology Research·Liang-Chuan S WangLai-Ming Ching

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Citations

Mar 23, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Holly L RosenzweigMichael P Davey
May 24, 2012·Chemical Reviews·Kye-Simeon Masters, Stefan Bräse
Jan 1, 2010·Acta Crystallographica. Section E, Structure Reports Online·Shi-Jie Zhang, Wei-Xiao Hu
Dec 15, 2010·American Journal of Respiratory Cell and Molecular Biology·Guanjun ChengSteven M Albelda
Mar 2, 2011·Journal of Leukocyte Biology·Howard Young
Mar 14, 2013·British Journal of Cancer·Z G FridlenderS M Albelda

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