title: Effects of transferrin conjugates of artemisinin and artemisinin dimer on breast cancer cell lines.
abstract: Transferrin (Tf) conjugates of monomeric artemisinin (ART) and artemisinin dimer were synthesized. The two conjugates, ART-Tf and dimer-Tf, retained the original protein structure, and formed stable aggregates in aqueous buffer. ART-Tf induced declines in proteins involved in apoptosis (survivin), cell cycling (cyclin D1), oncogenesis (c-myelocytomatosis oncogene product (c-MYC)), and dysregulated WNT signaling (beta-catenin) in both the human prostate (DU145) and breast (MCF7) cancer cell lines. Both ART-Tf and dimer-Tf induced down-regulation of survivin, c-MYC and mutated human epidermal growth factor receptor-2 (ERBB2 or HER2) in the BT474 breast cancer cell line. To our knowledge, this is the first demonstration that an ART derivative can cause a decline of ERBB2 in a human cancer cell line. Potential mechanisms for the observed effects are presented. Both transferrin conjugates strongly inhibited the growth of BT474 cells in the same concentration range that the conjugates caused declines in the levels of ERBB2, survivin, and c-MYC, while showing essentially no toxicity towards MCF10A normal breast cells.
authors.affiliation: Department of Chemistry, Box 351700, University of Washington, Seattle, WA 98195-1700, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Gong
authors.forename: Byron M
authors.initials: BM
authors.lastname: Gallis
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Hailing
authors.initials: H
authors.lastname: Lu
authors.forename: Eric
authors.initials: E
authors.lastname: Lacoste
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 / Q000008:administration & dosage / Q000737:chemistry; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D000077022:Survivin; D014168:Transferrin / Q000008:administration & dosage / Q000737:chemistry; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D037621:Artemisinins; D019938:Cyclin D1; D051034:Inhibitor of Apoptosis Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D000077022:Survivin; D014168:Transferrin; D051176:beta Catenin; C107489:BIRC5 protein, human; C530104:CCND1 protein, human; C489427:MYC protein, human; C031327:artemisinin; C508053:ERBB2 protein, human