2-deoxy-D-glucose reduces the level of constitutive activation of ATM and phosphorylation of histone H2AX.

Cell Cycle
Toshiki TanakaZbigniew Darzynkiewicz

Abstract

Histone H2AX phosphorylated on Ser-139, defined as gammaH2AX, is a reporter of DNA double-strand breaks (DSBs). While H2AX undergoes phosphorylation after induction of DNA damage by genotoxic agents or during physiological events that involve DNA recombination, it also is phosphorylated in untreated normal and tumor cells. We recently reported that this constitutive H2AX phosphorylation (CHP) is markedly reduced by the antioxidant N-acetyl-L-cysteine (NAC), and postulated that it reflects the oxidative DNA damage ("endogenous DSBs") induced by reactive oxygen species (ROS) generated by metabolic activity during progression through the cell cycle. In the present study, we provide evidence that growth of cells from three human lymphoblastoid cell lines TK6, NH32 and WTK1 in the presence of the glucose antimetabolite 2-deoxy-D-glucose (2-DG) led to a distinct reduction in the level of CHP. The reduction of CHP was more pronounced in S and G(2)M than in G(1) phase cells. Constitutive activation of ATM was also reduced. The data suggest that a decrease in a cell's metabolic activity as a result of inhibition of glycolysis by 2-DG reduces generation of ROS which leads to the reduction of oxidative DNA damage. The data also point out ...Continue Reading

Citations

Jan 15, 2009·Nature Reviews. Cancer·Nicholas C Denko
Jan 12, 2012·Molecular Cancer Therapeutics·Evan Noch, Kamel Khalili
Jul 12, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Toshiki TanakaZbigniew Darzynkiewicz
Sep 20, 2007·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Jul 13, 2013·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·K BerniakJ W Dobrucki
Sep 10, 2011·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Oct 13, 2010·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Hong ZhaoZbigniew Darzynkiewicz
Mar 29, 2014·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Zbigniew DarzynkiewiczJoseph M Wu
Apr 12, 2015·Breast Cancer Research and Treatment·Merve AlpayKevin D Brown

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