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Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from pro-survival to pro-apoptosis

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Abstract

Selenium at low concentrations has a chemopreventive role against cancer, while at high concentrations, selenite exerts a direct antitumor effect. However, the mechanisms behind these effects remain elusive. In this study, we found that different concentrations of selenite triggered different signal pathways in human leukemia NB4 cells. Low concentrations of selenite elicited mild endoplasmic reticulum (ER) stress and mediated cell survival by activating unfolded protein response signaling, whereas high concentrations of selenite induced severe ER stress and caused cell death by activation of the pro-apoptotic transcription factors GADD153. In addition, selenite at low concentrations activated other anti-apoptotic pathways, such as AKT and ERK, whereas high concentrations of selenite induced activation of p53 and oxidative stress, which mediated the antitumor activity of selenite by causing mitochondrial dysfunction and caspase activation. These findings uncover the molecular mechanisms of the chemopreventive and antitumor effects of different concentrations of selenite.

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Acknowledgments

This work was supported by grants from National Natural Sciences Foundation of China (no. 30370348 and no. 30770491), Doctoral Point Foundation of National Educational Committee (no. 20010023029), and Natural Sciences Foundation of Beijing (no. 7032034 and no. 5082015).

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Authors and Affiliations

  1. National Laboratory of Medical Molecular Biology, Institute of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100005, People’s Republic of China

    Liying Guan, Bingshe Han, Zhushi Li, Fang Huang, Yang Yang & Caimin Xu

  2. Department of Hematology, Peking Union Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

    Jian Li

  3. Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, CAMS & PUMC, 5 Dongdan Santiao, Dongcheng District, Beijing, 100005, China

    Caimin Xu

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  1. Liying Guan
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Correspondence to Caimin Xu.

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Guan, L., Han, B., Li, J. et al. Exposure of human leukemia NB4 cells to increasing concentrations of selenite switches the signaling from pro-survival to pro-apoptosis. Ann Hematol 88, 733–742 (2009). https://doi.org/10.1007/s00277-008-0676-4

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