Targeting cancer cells with transferrin conjugates containing the non-toxic type 2 ribosome-inactivating proteins nigrin b or ebulin l

• Published in: Cancer letters Vol. 184; no. 1; pp. 29 - 35
• Main Authors: Citores, Lucı́a, Miguel Ferreras, J., Muñoz, Raquel, Benı́tez, Jorge, Jiménez, Pilar, Girbés, Tomás
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 08.10.2002; Elsevier Limited
• Subjects: Animals; Apoptosis; Binding sites; Cancer; Cancer therapies; Cancer therapy; Chromatography; Construction; Drug Delivery Systems; Ebulin l; HeLa cells; HeLa Cells - drug effects; HeLa Cells - metabolism; Humans; N-Glycosyl Hydrolases - pharmacology; Nigrin b; Plant Proteins - pharmacology; Polypeptides; Protein synthesis; Protein Synthesis Inhibitors - pharmacology; Proteins; Rabbits; Receptors, Transferrin - metabolism; Ribosome Inactivating Proteins, Type 2; Ribosome-inactivating proteins; Studies; Transferrin - pharmacology; Transferrin conjugates; SPDP, N-succinimidyl-3-(2-pyridyldithio)propionate; Ribosome-inactivating proteins; IC50, concentration of inhibitor that gives 50% inhibition of protein synthesis; Nigrin b; TfR, transferrin receptor; MBS, m-maleimido-benzoyl-N-hydroxysuccinimidyl ester; HARA, human anti-ricin antibodies; Cancer therapy; 2-IT, 2-iminothiolane; HeLa cells; RIP, ribosome-inactivating protein; Transferrin conjugates; Ebulin l; Tf, transferrin
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(02)00169-6

Nigrin b and ebulin l are type 2 ribosome-inactivating proteins (RIPs) with 104 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 IC50 of the proteins from 3×10−7M (nigrin b) and 1.5×10−8M (ebulin l) to 3.5×10−10M in HeLa cells. Thus, both conjugates could be considered as useful tools for targeting TfR-over-expressing cancer cells.