title: Dihydroartemisinin induces autophagy and inhibits the growth of iron-loaded human myeloid leukemia K562 cells via ROS toxicity.
abstract: 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 G2/M phase.
authors: Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou Zhejiang 310058, People's Republic of China ; Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou 310022, People's Republic of China.
authors: Zeng
authors: Z
authors: Wang
authors: Wei
authors: W
authors: Hu
authors: Jia-Li
authors: JL
authors: Zhang
authors: Xiu-Hua
authors: XH
authors: Wu
authors: Hui-Jun
authors: HJ
authors: Zhou
keywords: AO, acridine orange; DHA, dihydroartemisinin; Dihydroartemisinin; EB, ethidium bromide; Iron; K562 cell; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Mitophagy; PARP, poly(ADP-ribose) polymerases; PBS, phosphate buffer saline; ROS; ROS, reactive oxygen species; TfR, transferrin receptor
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