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.
FEBS Open Bio. 2012 May 23;2:103-12. doi: 10.1016/j.fob.2012.05.002. Print 2012.
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.
二氢青蒿素（DHA）是青蒿素衍生物的一种活性代谢物，是最显著的抗疟药物，对人体毒性很小。最近的研究表明，DHA 能有效抑制癌细胞的生长。在本研究中，我们旨在阐明 DHA 抑制负载铁的人髓性白血病 K562 细胞生长的机制。线粒体是自噬和细胞凋亡的重要调节因子，线粒体功能障碍的一个触发因素是活性氧（ROS）的产生。我们发现，DHA 诱导的白血病 K562 细胞自噬，其细胞内细胞器主要是线粒体，依赖于 ROS。这些细胞的自噬伴随着 LC3-II 蛋白表达和 caspase-3 激活。此外，我们还证明 DHA 抑制白血病 K562 细胞的增殖也依赖于铁。这种抑制包括 TfR 表达的下调和 K562 细胞在 G2/M 期的生长停滞。
