Hydrogen peroxide is often required in sublethal, millimolar concentrations to show its
oxidant effects on cells in culture as it is easily destroyed by cellular
catalase. Previously, we had shown that
diperoxovanadate, a physiologically stable peroxovanadium compound, can substitute H2O2 effectively in peroxidation reactions. We report here that
peroxovanadate when anchored to
polyacrylic acid (PAPV) becomes a highly potent inhibitor of growth of lung
carcinoma cells (A549). The early events associated with PAPV treatment included cytoskeletal modifications, increase in
GTPase activity of Rac1, accumulation of the
reactive oxygen species, and also increase in phosphorylation of H2AX (γH2AX), a marker of DNA damage. These effects persisted even at 24 h after removal of the compound and culminated in increased levels of p53 and p21 together with growth arrest. The PAPV-mediated growth arrest was significantly abrogated in cells pre-treated with the
N-acetylcysteine, Rac1 knocked down by
siRNA and DPI an inhibitor of
NADPH oxidase. In conclusion, our results show that polyacrylate derivative of
peroxovanadate efficiently arrests growth of A549 cancerous cells by activating the axis of Rac1-NADPH
oxidase leading to oxidative stress and DNA damage.