Abstract B84: NADPH oxidase 1 (NOX1) and related NOX isoforms as key mediators of NFB signaling in colon cancer Academic Article uri icon


  • Abstract B84 NADPH oxidase/dual-oxidase (Nox/Duox) family members have been implicated in nuclear factor kappa-B (NFB)-mediated inflammation and inflammation-associated pathologies. In rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) alternating with a high-fat diet, Nox1, Nox4 and Duo2, but not Nox2, were over-expressed in colon tumors at 1 year, as shown by quantitative RT-PCR and immunoblotting. Over-expression of Nox/duox isoforms coincided with increased nuclear NFB protein, and elevated levels of downstream targets IL-1, IL6, TNF- and TNFR1. Over-expression of Nox1 and activation of NFB also occurred at early stages of colon carcinogenesis, prior to tumor development. Nox/Duox isoforms were over-expressed in primary human colon cancers and in several human colorectal cancer cell lines. In HT29 cells, silencing of Nox1 inhibited nuclear translocation and DNA binding activity of NFB, attenuated downstream targets IL1, c-myc, and cyclin D1, and blocked lipopolysaccharide-induced phosphorylation of IB kinase/, resulting in G1 arrest. We conclude that the Nox1-NFB pathway is important in colon tumorigenesis, and that Nox1 may provide a target for novel therapeutic strategies against colon cancer development. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B84.

published proceedings

  • Cancer Prevention Research

author list (cited authors)

  • Wang, R., Dashwood, W., Nian, H., Tsuchiya, N., Nakagama, H., & Dashwood, R.

complete list of authors

  • Wang, Rong||Dashwood, Wan-Mohaiza||Nian, Hui||Tsuchiya, Naoto||Nakagama, Hitoshi||Dashwood, Roderick

publication date

  • November 2008