Cancer Lett. 2009 Feb 18;274(2):290-8. Epub 2008 Nov 8.
receptor-dependent cytotoxicity of artemisinin-transferrin conjugates
on prostate cancer cells and induction of apoptosis.
Nakase I, Gallis B, Takatani-Nakase T, Oh S, Lacoste E, Singh NP, Goodlett DR, Tanaka S, Futaki S, Lai H, Sasaki T.
Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA.
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.