Abstract
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.
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Abbreviations
- PAPV:
-
Polyacrylate-anchored peroxovanadate
- ROS:
-
Reactive oxygen species
- NAC:
-
N-acetylcysteine
- DPI:
-
Diphenyl iodonium
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Acknowledgments
The work was supported by grant from DBT under the North-East Twining program. We thank CDFD and ILBS for providing necessary infrastructure to carry out the work. TA is the recipient of Junior and Senior Research Fellowships of the University Grants Commission towards the pursuit of a PhD degree of the Manipal University. TR is a Hon. Scientist of the Indian National Science Academy, New Delhi.
Authors contribution
GR conceived the concept and designed experiments with NC. All the experiments were performed by NC. TA helped with senescence experiment. TR gave necessary inputs. NI prepared the peroxovanadate. TR, NC, GR wrote the manuscript together.
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An erratum to this article is available at http://dx.doi.org/10.1007/s11010-016-2844-5.
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Chatterjee, N., Anwar, T., Islam, N.S. et al. Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis. Mol Cell Biochem 420, 9–20 (2016). https://doi.org/10.1007/s11010-016-2761-7
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DOI: https://doi.org/10.1007/s11010-016-2761-7