title: Targeting cancer cells with transferrin conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrin b or ebulin l.
abstract: Nigrin b and ebulin l are type 2 ribosome-inactivating proteins (RIPs) with 10(4) times less cellular and in vivo toxicity than ricin that are currently being considered for the construction of anti-cancer conjugates. Here we provide evidence that both RIPs can be used for the construction of conjugates directed to a target such as the transferrin receptor (TfR), which is over-expressed in cancer cells. Nigrin b- and ebulin l-transferrin conjugates were constructed with no substantial reduction in the translational inhibitory molecular activity of either RIPs. Conjugation with transferrin decreased the IC(50) of the proteins from 3 x 10(-7)M (nigrin b) and 1.5 x 10(-8)M (ebulin l) to 3.5 x 10(-10)M in HeLa cells. Thus, both conjugates could be considered as useful tools for targeting TfR-over-expressing cancer cells.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Valladolid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Citores
authors.forename: J Miguel
authors.initials: JM
authors.lastname: Ferreras
authors.forename: Raquel
authors.initials: R
authors.lastname: Muñoz
authors.forename: Jorge
authors.initials: J
authors.lastname: Benítez
authors.forename: Pilar
authors.initials: P
authors.lastname: Jiménez
authors.forename: Tomás
authors.initials: T
authors.lastname: Girbés
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D011990:Receptors, Transferrin / Q000378:metabolism; D054790:Ribosome Inactivating Proteins, Type 2; D014168:Transferrin / Q000494:pharmacology*
chemical_list: D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D011990:Receptors, Transferrin; D054790:Ribosome Inactivating Proteins, Type 2; D014168:Transferrin; C107391:ebulin r protein, Sambucus ebulus; D009699:N-Glycosyl Hydrolases