Premium
Grape seed proanthocyanidins inhibit cigarette smoke condensate‐induced lung cancer cell migration through inhibition of NADPH oxidase and reduction in the binding of p22 phox and p47 phox proteins
Author(s) -
Vaid Mudit,
Katiyar Santosh K.
Publication year - 2015
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22173
Subject(s) - biology , nadph oxidase , proanthocyanidin , cigarette smoke , biochemistry , oxidase test , cancer research , microbiology and biotechnology , enzyme , antioxidant , toxicology , polyphenol
Cigarette smoking is the major cause of lung cancer. It is therefore important to develop effective strategies that target molecular abnormalities induced by cigarette smoke condensate (CSC). Cigarette smoking increases oxidative stress particularly via activation of NADPH oxidase (NOX), a key source of superoxide anion production. Here, we report that grape seed proanthocyanidins (GSPs) exert an inhibitory effect on the CSC‐induced migration of non‐small cell lung cancer (NSCLC) cells (A549, H460, and H1299). Using an in vitro invasion assay, we found that treatment of NSCLC cells with CSC increased NSCLC cell migration by enhancing NOX mediated‐oxidative stress. Treatment of NSCLC cells with GSPs inhibited the CSC‐induced cell migration through reduction in oxidative stress levels and a reduction in the epithelial‐to‐mesenchymal transition. To identify the molecular targets of GSPs, we examined the effects of GSPs on CSC‐induced alterations in the levels of key NOX components, namely p22 phox and p47 phox proteins, using A549 cells. We also determined the effect of GSPs on CSC‐induced interaction/binding between these proteins, which is a key event in NOX activation. We found that treatment of A549 cells with GSPs not only inhibited the CSC‐induced increase in the expression levels of p22 phox and p47 phox , but also reduced the binding of p22 phox to p47 phox proteins. This new insight into the anti‐lung cancer cell migration activity of GSPs could serve as a basis for development of improved chemopreventive or therapeutic strategies for lung cancer. © 2014 Wiley Periodicals, Inc.