期刊
CANCER LETTERS
卷 274, 期 2, 页码 290-298出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.09.023
关键词
Artemisinin; Transferrin; Anti-cancer; Transferrin receptor; Apoptosis
类别
资金
- Brady Natural Products
- Department of Medicinal Chemistry
- Ecogenetics and Environmental Health [ES0006-033]
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 similar to 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. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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