title: Transferrin receptor-dependent cytotoxicity of artemisinin-transferrin conjugates on prostate cancer cells and induction of apoptosis.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Washington, Seattle, WA 98195-1700, USA.
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.forename: Byron
authors.initials: B
authors.lastname: Gallis
authors.forename: Tomoka
authors.initials: T
authors.lastname: Takatani-Nakase
authors.forename: Steve
authors.initials: S
authors.lastname: Oh
authors.forename: Eric
authors.initials: E
authors.lastname: Lacoste
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Seigo
authors.initials: S
authors.lastname: Tanaka
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
authors.forename: Henry
authors.initials: H
authors.lastname: Lai
authors.forename: Tomikazu
authors.initials: T
authors.lastname: Sasaki
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin / Q000378:metabolism / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014168:Transferrin / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D037621:Artemisinins; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D014168:Transferrin; C031327:artemisinin