Enzyme prodrug therapy designed to target L-methioninase to the tumor vasculature.

A new approach for enzyme prodrug therapy for cancer was tested using human endothelial cells and two breast cancer cell lines in vitro. The concept is to use the human annexin V protein to selectively target the enzyme L-methioninase to the tumor vasculature. The major finding was that enzyme prodrug treatment using the L-methioninase-annexin V fusion protein and selenomethionine as the prodrug over 3 days was shown to be lethal to the endothelial cells and the cancer cells, while having little or no effect with the prodrug but with no fusion protein present.

Non-covalent attachment of proteins to single-walled carbon nanotubes.

A method for the non-covalent attachment of proteins to single-walled carbon nanotubes (SWNTs) is described. In this method, the protein is adsorbed to SWNTs that are suspended using sodium cholate, a surfactant and bile salt. The sodium cholate is then removed by dialysis with retention of the protein on the SWNTs.

Selective growth inhibition of cancer cells by L-methioninase-containing fusion protein targeted to the urokinase receptor.

Background: We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines.

Methods: The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods.

Influence of L-methioninase targeted to the urokinase receptor on the proliferation and motility of lung and prostate cancer cells.

Background: Previously, we reported that a novel fusion protein consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase inhibited MCF-7 breast cancer cells in vitro to a greater extent than treatment with L-methioninase.

Materials And Methods: The fusion protein, L-methioninase and a mutated fusion protein without L-methioninase activity were produced by recombinant methods. The effects of fusion protein, L-methioninase, and mutated fusion protein treatment on the proliferation and motility of SK-LU-i lung and PC-3 prostate and cancer cells were measured in vitro using a culture wounding assay.

Targeting a methioninase-containing fusion protein to breast cancer urokinase receptors inhibits growth and migration.

Background: We previously reported that a novel fusion protein (consisting of an amino-terminal fragment of urokinase which binds to the urokinase receptor, and L-methioninase which depletes methionine and arrests the growth of methionine-dependent tumors) inhibited MCF-7 breast cancer cells in vitro.

Materials And Methods: We produced this fusion protein, L-methioninase, and a mutated fusion protein without L-methioninase activity by recombinant methods. MCF-7 cell proliferation and mobility were measured in vitro in a culture wounding assay.