Action of Fenretinide (4-HPR) on Ovarian Cancer and Endothelial Cells

• Published in: Anticancer research 2005-01, Vol.25 (1A), p.249-253
• Main Authors: GOLUBKOV, Vladislav, GARCIA, Agustin, MARKLAND, Francis S
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Angiogenesis Inhibitors - pharmacology; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - enzymology; Female; Female genital diseases; Fenretinide - pharmacology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Neoplasm Invasiveness; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - enzymology; Neovascularization, Pathologic - pathology; Ovarian Neoplasms - blood supply; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Phosphorylation - drug effects; Protein-Tyrosine Kinases - metabolism; Tumors; Umbilical Veins - cytology
• ISSN: 0250-7005; 1791-7530

Background: Fenretinide (4-HPR) is a synthetic retinoid that has been reported to inhibit the growth of cancer cell lines in vitro. Materials and Methods: We examined the effect of 4-HPR on ovarian cancer (OVCAR-5) cell proliferation, viability and invasion using standard techniques. We also examined the action of 4-HPR on the actin cytoskeleton using immunocytochemistry, and on phosphorylation of focal adhesion kinase (FAK) using immunoprecipitation and phosphotyrosine immunoblotting. We then examined the activity of 4-HPR on endothelial cells using the tube formation assay on Matrigel. Results: 4-HPR inhibited OVCAR-5 cell proliferation and viability at concentrations higher than 1 μM, with 70-90% growth inhibition at 10 μM. 4-HPR (1 μM) significantly inhibited OVCAR-5 invasion after 3 days preincubation. In view of the importance of the cytoskeleton in cell motility, we examined the action of 4-HPR on the actin cytoskeleton and on FAK phosphorylation. In OVCAR-5 cells treated with 1 mM fenretinide for 3 days, actin cytoskeleton stress fibers were disrupted and FAK tyrosine phosphorylation was elevated dose-dependently. Endothelial cells treated with 1 μM 4-HPR failed to form tubes, but formed small cellular aggregates. Conclusion: Fenretinide has anti-tumor activity by acting on the actin cytoskeleton and by regulating FAK tyrosine phosphorylation. 4-HPR also inhibits endothelial cell tube formation, a major step in angiogenesis.