NDLI: A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells

Content Provider	PubMed Central
Author	Gianni, Davide Taulet, Nicolas Zhang, Hui Celine, Dermardirossian Kister, Jeremy Martinez, Luis Roush, William R. Brown, Steve J. Bokoch, Gary M. Rosen, Hugh
Abstract	The NADPH oxidase (Nox) proteins catalyze the regulated formation of reactive oxygen species (ROS) which play key roles as signaling molecules in several physiological and pathophysiological processes. ROS generation by the Nox1 member of the Nox family is necessary for the formation of extracellular matrix (ECM)-degrading, actin-rich cellular structures known as invadopodia. Selective inhibition of Nox isoforms can provide reversible, mechanistic insights into these cellular processes in contrast to scavenging or inhibition of ROS production. Currently no specific Nox inhibitors have been described. Here, by high-throughput screening, we identify a sub-set of phenothiazines, 2-acetylphenothiazine (here referred to as ML171) (and its related 2-(trifluoromethyl)-phenothiazine) as nanomolar, cell-active and specific Nox1 inhibitors that potently block Nox1-dependent ROS generation, with only marginal activity on other cellular ROS-producing enzymes and receptors including the other Nox isoforms. ML171 also blocks the ROS-dependent formation of ECM-degrading invadopodia in colon cancer cells. Such effects can be reversed by overexpression of Nox1 protein, which is suggestive of a selective mechanism of inhibition of Nox1 by this compound. These results elucidate the relevance of Nox1-dependent ROS generation in mechanisms of cancer invasion, and define ML171 as a useful Nox1 chemical probe and a potential therapeutic agent for inhibition of cancer cell invasion.
Related Links	http://dx.doi.org/10.1021/cb100219n
Ending Page	993
Page Count	13
Starting Page	981
File Format	PDF
ISSN	15548929
e-ISSN	15548937
Journal	ACS chemical biology
Issue Number	10
Volume Number	5
Language	English
Publisher Date	2010-10-15
Access Restriction	Open
Subject Keyword	Molecular Medicine Biochemistry Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Molecular Medicine

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor

Novel p47phox-related organizers regulate NADPH oxidase 1 (Nox1) activity and localization

Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes

p47phox and NOXO1, the Organizer Subunits of the NADPH Oxidase 2 (Nox2) and NADPH Oxidase 1 (Nox1)

A Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In vitro and In vivo

A Small-molecule Inhibitor, 5′-O-Tritylthymidine, targets FAK and Mdm-2 Interaction, and Blocks Breast and Colon Tumorigenesis in vivo

Novel Small-Molecule Inhibitor of Apurinic/Apyrimidinic Endonuclease 1 Blocks Proliferation and Reduces Viability of Glioblastoma CellsS⃞

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells

c-Src–Mediated Phosphorylation of NoxA1 and Tks4 Induces the Reactive Oxygen Species (ROS)–Dependent Formation of Functional Invadopodia in Human Colon Cancer Cells

A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells

Similar Documents

Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor

Novel p47phox-related organizers regulate NADPH oxidase 1 (Nox1) activity and localization

Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes

p47phox and NOXO1, the Organizer Subunits of the NADPH Oxidase 2 (Nox2) and NADPH Oxidase 1 (Nox1)

A Novel Small-Molecule Inhibitor of Mcl-1 Blocks Pancreatic Cancer Growth In vitro and In vivo

A Small-molecule Inhibitor, 5′-O-Tritylthymidine, targets FAK and Mdm-2 Interaction, and Blocks Breast and Colon Tumorigenesis in vivo

Novel Small-Molecule Inhibitor of Apurinic/Apyrimidinic Endonuclease 1 Blocks Proliferation and Reduces Viability of Glioblastoma CellsS⃞

A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells

c-Src–Mediated Phosphorylation of NoxA1 and Tks4 Induces the Reactive Oxygen Species (ROS)–Dependent Formation of Functional Invadopodia in Human Colon Cancer Cells

A novel and specific NADPH oxidase-1 (Nox1) small-molecule inhibitor blocks the formation of functional invadopodia in human colon cancer cells