methaneselenol and Breast-Neoplasms

The L-methioninase-annexin V/selenomethionine enzyme prodrug system, designed to target the tumor vasculature and release the methylselenol anticancer drug in the tumor, was tested in mice with implanted MBA-MB-231 breast tumors. This therapy was able to cause a reduction in the size of the tumors during the treatment period. It was shown that L-methioninase-annexin V was uniformly bound at the blood vessel surface in the tumor and also that there was a substantial cutoff of blood flowing through the treated tumor, consistent with the therapy's design. This new approach for enzyme prodrug therapy of breast cancer appears promising.

Topics: Animals; Annexin A5; Antineoplastic Agents; Breast Neoplasms; Carbon-Sulfur Lyases; Cell Line, Tumor; Enzyme Therapy; Female; Humans; Mammary Neoplasms, Animal; Methanol; Mice; Mice, SCID; Neoplasm Transplantation; Organoselenium Compounds; Prodrugs; Selenomethionine

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. Thus, this new approach appears promising.

Topics: Annexin A5; Breast Neoplasms; Carbon-Sulfur Lyases; Cell Line; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Endothelial Cells; Female; Humans; Kinetics; Methanol; Neovascularization, Pathologic; Organoselenium Compounds; Prodrugs; Protein Binding; Recombinant Fusion Proteins; Selenomethionine