Journal
FEBS OPEN BIO
Volume 2, Issue -, Pages 103-112Publisher
WILEY
DOI: 10.1016/j.fob.2012.05.002
Keywords
Dihydroartemisinin; ROS; Mitophagy; K562 cell; Iron
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Funding
- National Natural Science Foundation of China [81072659]
- Zhejiang Provincial Science and Technology Program, China [2008C23067]
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Dihydroartemisinin (DHA), an active metabolite of artemisinin derivatives, is the most remarkable anti-malarial drug and has little toxicity to humans. Recent studies have shown that DHA effectively inhibits the growth of cancer cells. In the present study, we intended to elucidate the mechanisms underlying the inhibition of growth of iron-loaded human myeloid leukemia K562 cells by DHA. Mitochondria are important regulators of both autophagy and apoptosis, and one of the triggers for mitochondrial dysfunction is the generation of reactive oxygen species (ROS). We found that the DHA-induced autophagy of leukemia K562 cells, whose intracellular organelles are primarily mitochondria, was ROS dependent. The autophagy of these cells was followed by LC3-II protein expression and caspase-3 activation. In addition, we demonstrated that inhibition of the proliferation of leukemia K562 cells by DHA is also dependent upon iron. This inhibition includes the down-regulation of TfR expression and the induction of K562 cell growth arrest in the G(2)/M phase. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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