Nakase Ikuhiko, Gallis Byron, Takatani-Nakase Tomoka, Oh Steve, Lacoste Eric, Singh Narendra P, Goodlett David R, Tanaka Seigo, Futaki Shiroh, Lai Henry, Sasaki Tomikazu
Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA.
Cancer Lett. 2009 Feb 18;274(2):290-8. doi: 10.1016/j.canlet.2008.09.023. Epub 2008 Nov 8.
Artemisinin, a natural product isolated from Artemisia annua, contains an endoperoxide group that can be activated by intracellular iron to generate toxic radical species. Cancer cells over-express transferrin receptors (TfR) for iron uptake while most normal cells express nearly undetectable levels of TfR. We prepared a series of artemisinin-tagged transferrins (ART-Tf) where different numbers of artemisinin units are attached to the N-glycoside chains of transferrin (Tf). The Tf bearing approximately 16 artemisinins retains the functionality of both Tf and artemisinin. Reduction of TfRs by TfR siRNA transfection significantly impaired the ability of ART-Tf, but not dihydroartemisinin, to kill cells. We also demonstrate that the ART-Tf conjugate kills the prostate carcinoma cell line DU 145 by the mitochondrial pathway of apoptosis.
青蒿素是从黄花蒿中分离出的一种天然产物，含有一个内过氧化物基团，该基团可被细胞内的铁激活，生成有毒的自由基。癌细胞过度表达转铁蛋白受体（TfR）以摄取铁，而大多数正常细胞表达的TfR水平几乎检测不到。我们制备了一系列青蒿素标记的转铁蛋白（ART-Tf），其中不同数量的青蒿素单元连接到转铁蛋白（Tf）的N-糖苷链上。带有大约16个青蒿素的Tf保留了Tf和青蒿素的功能。通过TfR siRNA转染降低TfRs显著损害了ART-Tf而非双氢青蒿素杀死细胞的能力。我们还证明，ART-Tf偶联物通过线粒体凋亡途径杀死前列腺癌细胞系DU 145。
