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Dimethylfumarate induces cell cycle arrest and apoptosis via regulating intracellular redox systems in HeLa cells

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An Erratum to this article was published on 14 October 2016

Abstract

Dimethylfumarate (DMF) is cytotoxic to several kinds of cells and serves as an anti-tumor drug. This study was designed to investigate the effects and underlying mechanism of DMF on cervical cancer cells. HeLa cells were cultured and treated with 0, 50, 100, 150, and 200 μM DMF, respectively. After 24 h, cell growth was evaluated using Cell Counting Kit-8 (CCK-8) assay and the cell cycle was examined using flow cytometry. In addition, cell apoptosis was detected by Annexin V/propidium iodide (PI) staining and the expressions of caspase-3 and poly-ADP-ribose polymerase (PARP) were detected using western blotting. The redox-related factors were then assessed. Furthermore, all of the indicators were detected in HeLa cells after combined treatment of DMF and N-acetyl-l-cysteine (NAC, an oxygen-free radical scavenger). The cell number and cell growth of HeLa were obviously inhibited by DMF in a dose-dependent manner, as the cell cycle was arrested at G0/G1 phase (P < 0.05). The apoptotic HeLa cells were markedly increased, and the expression levels of caspase-3 and PARP were significantly increased in a DMF concentration-dependent way (P < 0.05). Meanwhile, loss of △Ψm, increase in reactive oxygen species and O2 ·−, and the decrease in catalase activity and glutathione (GSH) level were found after DMF treatment (P < 0.05). All these changes were significantly attenuated and even completely disappeared by adding NAC (P < 0.05). In conclusion, the cytotoxicity of DMF on cell proliferation and apoptosis of HeLa cells was mainly related to the intracellular redox systems by depletion of intracellular GSH.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 81573057) and Education Bureau of Zhejiang Province (Grant No. Y201430634).

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Authors and Affiliations

  1. Department of Radiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, People’s Republic of China

    Guocan Han

  2. Department of Dermatology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, 3 Qingchun Road East, Hangzhou, 310016, People’s Republic of China

    Qiang Zhou

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  1. Guocan Han
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  2. Qiang Zhou
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Correspondence to Qiang Zhou.

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Editor: Tetsuji Okamoto

An erratum to this article is available at http://dx.doi.org/10.1007/s11626-016-0094-1.

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Han, G., Zhou, Q. Dimethylfumarate induces cell cycle arrest and apoptosis via regulating intracellular redox systems in HeLa cells. In Vitro Cell.Dev.Biol.-Animal 52, 1034–1041 (2016). https://doi.org/10.1007/s11626-016-0069-2

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