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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 7409196, 14 pages
Research Article

Apocynin and Diphenyleneiodonium Induce Oxidative Stress and Modulate PI3K/Akt and MAPK/Erk Activity in Mouse Embryonic Stem Cells

1Institute of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 267/2, 61137 Brno, Czech Republic
2Institute of Biophysics, Academy of Sciences of the Czech Republic, Královopolská 2590/135, 61200 Brno, Czech Republic
3Department of Histology and Embryology, Faculty of Medicine, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic
4International Clinical Research Center, Center of Biomolecular and Cellular Engineering, St. Anne’s University Hospital, Pekařská 53, 65691 Brno, Czech Republic

Received 12 August 2015; Accepted 13 September 2015

Academic Editor: Tomris Ozben

Copyright © 2016 Jan Kučera et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Reactive oxygen species (ROS) are important regulators of cellular functions. In embryonic stem cells, ROS are suggested to influence differentiation status. Regulated ROS formation is catalyzed primarily by NADPH-dependent oxidases (NOXs). Apocynin and diphenyleneiodonium are frequently used inhibitors of NOXs; however, both exhibit uncharacterized effects not related to NOXs inhibition. Interestingly, in our model of mouse embryonic stem cells we demonstrate low expression of NOXs. Therefore we aimed to clarify potential side effects of these drugs. Both apocynin and diphenyleneiodonium impaired proliferation of cells. Surprisingly, we observed prooxidant activity of these drugs determined by hydroethidine. Further, we revealed that apocynin inhibits PI3K/Akt pathway with its downstream transcriptional factor Nanog. Opposite to this, apocynin augmented activity of canonical Wnt signaling. On the contrary, diphenyleneiodonium activated both PI3K/Akt and Erk signaling pathways without affecting Wnt. Our data indicates limits and possible unexpected interactions of NOXs inhibitors with intracellular signaling pathways.