Action of fenretinide (4-HPR) on ovarian cancer and endothelial cells

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 microM, with 70-90% growth inhibition at 10 microM. 4-HPR (1 microM) 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 microM 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.