Fenretinide

Fenretinide (4-HPR) is a synthetic retinoid deriverative. 4-HBR is shown to exhibit binding to the retinoic acid receptors (RAR) at concentrations necessary to induce cell death. (In Vitro) :Fenretinide (4-HPR) exerts not just acute but also long term antitumor activity in selected T-ALL cell lines. Fenretinide inhibits DES activity in CCRF-CEM leukemia cells in a dose and time dependent manner, leading to a concomitant increase of the endogenous cellular dhCer content. Fenretinide (3 μM) -induced dhCer accumulation in both CCRF-CEM and Jurkat cells. Ceramide inhibition with fenretinide protects insulin signaling. Fenretinide prevents lipid-induced reductions in insulin-stimulated glucose uptake. Fenretinide inhibits OVCAR-5 cell proliferation and viability at concentrations higher than 1 microM, with 70-90% growth inhibition at 10 microM. Fenretinide (1 microM) significantly inhibits OVCAR-5 invasion after 3 days preincubation. Endothelial cells treated with 1 microM 4-HPR fails to form tubes, but forms small cellular aggregates. (In Vivo) :Fenretinide (4-HPR) (10 mg/kg, i.p.) selectively inhibits ceramide accumulation HFD-fed male C57Bl/6 mice. Fenretinide treatment improves glucose tolerance and insulin sensitivity as determined by both glucose and insulin tolerance tests. Addition of 25 mg/kg ketoconazole to Fenretinide in NOD/SCID mice increased 4-HPR plasma levels.