IDIBELL researchers demonstrate for the first time that inhibition of NADPH oxidases pathway slows the growth of tumor cells in vitro A study realized by researchers at the IDIBEL has shown that a drug that is under evaluation for cardiovascular disease, VAS2870, inhibits in vitro the enzymes of the family of NADPH oxidases in liver tumor cells. So it is able to reduce cell growth and regain the ability of the cell to self-destruct (apoptosis) in response to TGF-beta factor. The study results were published at the journal Biochemical Pharmacology.
Hepatocellular carcinoma is the fifth most common cancer in the world wide and the third cause of cancer-related death globally. The origin of this tumor is associated with several molecular alterations; the most obvious is alteration of the mechanisms that regulate the balance between proliferation and cell death
NADPH oxidases
Proteins that form part of the family of NADPH oxidases have several functions, including cell signaling, regulation of gene expression and differentiation, growth and cell death. Previously, the research group led by Isabel Fabregat, had already demonstrated the relationship between NADPH oxidases and growth of liver tumor cells by activation of the epidermal growth factor receptor (EGFR) pathway.
The aim of this study is to investigate whether the inhibition of NADPH oxidases by a new drug (the VAS2870) is effective in countering the growth of tumor cells. Both antiproliferative activities (which slow the growth of cancer cells) and apoptotic ones (that stimulate self-destruction), were evaluated in tumor cells of rat liver and human. The results show that the action of VAS2870 blocks the growth of tumor cells and enhances their response to the apoptotic signal of TGF-beta, which lead them to self-destruct.
Isabel fabregat, researcher at Biological Clues of the Invasive and Metastatic Phenotype of IDIBELL and professor at the Faculty of Medicine, University of Barcelona and Patricia Sancho, post-doctoral researcher of the group, co-authors of the study, have highlighted the discovery of this new mechanism to find new drugs that slow the growth of liver tumors. In this line has said that “the VAS2870 is a good candidate for being tested in preclinical studies.”
Article reference
Sancho P., Fabregat I. The NADPH oxidase inhibitor VAS2870 impairs cell growth and enhances TGF-B-induced apoptosis of liver tumor cells. Biochemical Pharmacology (2011), doi:10.1016/j.bcp.2011.01.007. 2011 Apr. 1, 81 (7): 917-24