RGD Reference Report - The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-beta-induced apoptosis of liver tumor cells. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-beta-induced apoptosis of liver tumor cells.

Authors: Sancho, P  Fabregat, I 
Citation: Sancho P and Fabregat I, Biochem Pharmacol. 2011 Apr 1;81(7):917-24. Epub 2011 Jan 26.
RGD ID: 5131479
Pubmed: PMID:21276422   (View Abstract at PubMed)
DOI: DOI:10.1016/j.bcp.2011.01.007   (Journal Full-text)

Liver tumor cells show several molecular alterations which favor pro-survival signaling. Among those, we have proposed the NADPH oxidase NOX1 as a prosurvival signal for liver tumor cells. On the one side, we have described that FaO rat hepatoma cells show NOX1-dependent partial resistance to apoptosis induced by Transforming Growth Factor beta (TGF-beta). On the other side, we have shown that FaO cells, as well as different human hepatocellular carcinoma (HCC) cell lines, are able to proliferate in the absence of serum through the activation of a NOX1-dependent signaling pathway. The aim of this work was to analyze the effects of NADPH oxidase pharmacological inhibition in liver tumor cells using the inhibitor VAS2870. This compound inhibits dose-dependently autocrine increase of cell number in FaO rat hepatoma cells, and almost completely blocked ROS production and thymidine incorporation when used at 25muM. Such inhibitory effect on autocrine growth is coincident with lower mRNA levels of EGFR (Epidermal Growth Factor Receptor) and its ligand TGF-alpha (Transforming Growth Factor-alpha), and decreased phosphorylation of the EGFR itself and other downstream targets, such as SRC or AKT. Moreover, NADPH oxidase pharmacological inhibition also effectively attenuates serum-dependent growth and phosphorylation of AKT and ERK. Importantly, these inhibitory effects on either autocrine or serum-dependent cell growth are observed in several human HCC cell lines. Finally, we have observed that VAS2870 is also effective in enhancing apoptosis induced by a physiological stimulus, such as TGF-beta. In summary, NADPH oxidase pharmacological inhibition could be considered a promising tool in the treatment of liver cancer.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to xenobiotic stimulus  IEP 5131479NADPH oxidase inhibitors VAS2870 and apocyninRGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)


Additional Information