Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis

Chatterjee, Nirupama and Anwar, Tarique and Islam, Nashreen S and Ramasarma, T and Ramakrishna, Gayatri (2016) Growth arrest of lung carcinoma cells (A549) by polyacrylate-anchored peroxovanadate by activating Rac1-NADPH oxidase signalling axis. In: MOLECULAR AND CELLULAR BIOCHEMISTRY, 420 (1-2). pp. 9-20.

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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 (gamma H2AX), 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.

Item Type:	Journal Article
Publication:	MOLECULAR AND CELLULAR BIOCHEMISTRY
Additional Information:	The Copyright for this article belongs to Springer New York LLC
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	22 Oct 2016 10:14
Last Modified:	26 May 2022 11:26
URI:	https://eprints.iisc.ac.in/id/eprint/55089

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