Journal
ANNALS OF HEMATOLOGY
Volume 88, Issue 8, Pages 733-742Publisher
SPRINGER
DOI: 10.1007/s00277-008-0676-4
Keywords
Selenite; UPR; ER stress; Survival; Apoptosis
Categories
Funding
- National Natural Sciences Foundation of China [30370348, 30770491]
- Doctoral Point Foundation of National Educational Committee [20010023029]
- Natural Sciences Foundation of Beijing [7032034, 5082015]
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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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