Influence of L-Methioninase Targeted to the Urokinase Receptor on the Proliferation and Motility of Lung and Prostate Cancer Cells

• Published in: Anticancer research 2007-09, Vol.27 (5A), p.3435-3439
• Main Authors: PALWAI, Naveen R, ZANG, Xiao-Ping, HARRISON, Roger G, PENTO, J. Thomas
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Carbon-Sulfur Lyases - genetics; Carbon-Sulfur Lyases - pharmacology; Cell Growth Processes - drug effects; Cell Growth Processes - physiology; Cell Line, Tumor; Cell Movement - drug effects; Cell Movement - physiology; Drug Delivery Systems; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Medical sciences; Mutation; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Pneumology; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Urokinase Plasminogen Activator; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - pharmacology; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0250-7005; 1791-7530

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-1 lung and PC-3 prostate and cancer cells were measured in vitro using a culture wounding assay. Results: The fusion protein produced a dose-dependent inhibition of the proliferation and motility of both cancer cell lines. In addition, the fusion protein was found to be significantly more effective than L-methioninase alone or mutated fusion protein. Conclusion: Our results suggest that this fusion protein has potential as a selective therapeutic agent for the treatment of various methionine-dependent cancers.