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: Lucía Citores, J Miguel Ferreras, Raquel Muñoz, Jorge Benítez, Pilar Jiménez, Tomás Girbés
• Journal: Cancer letters (Cancer Lett) Vol. 184 Issue 1 Pg. 29-35 (Oct 08 2002) ISSN: 0304-3835 [Print] Ireland
• PMID: 12104045 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plant Proteins
• Protein Synthesis Inhibitors
• Receptors, Transferrin
• Ribosome Inactivating Proteins, Type 2
• Transferrin
• ebulin r protein, Sambucus ebulus
• N-Glycosyl Hydrolases

Topics

• Animals
• Drug Delivery Systems
• HeLa Cells (drug effects, metabolism)
• Humans
• N-Glycosyl Hydrolases (pharmacology)
• Plant Proteins (pharmacology)
• Protein Synthesis Inhibitors (pharmacology)
• Rabbits
• Receptors, Transferrin (metabolism)
• Ribosome Inactivating Proteins, Type 2
• Transferrin (pharmacology)