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.
摘要:
双氢青蒿素(DHA),青蒿素衍生物的活性代谢产物,是最引人注目的抗疟疾药物,对人类几乎没有毒性。最近的研究表明,DHA可以有效抑制癌细胞的生长。在本研究中,我们旨在阐明DHA抑制负载铁的人髓系白血病K562细胞生长的潜在机制。线粒体是自噬和凋亡的重要调节因子,线粒体功能障碍的触发因素之一是活性氧(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,是ROS依赖的。这些细胞的自噬随后是LC3-II蛋白表达和caspase-3激活。此外,我们证明DHA对白血病K562细胞增殖的抑制作用也依赖于铁。这种抑制包括TfR表达的下调和在G2/M期诱导K562细胞生长停滞。