Antioxidant Properties of N-(4-Hydroxyphenyl)retinamide (Fenretinide)

Abstract

Fenretinide, N-(4-Hydroxyphenyl)retinamide (4-HPR), is a cencer chemopreventive and antiproliferative agent whose mechanism of action is unknown. 4-HPR is a potent inducer of apoptosis in HL60 human leukemia cells which generates intracellular reactive oxygen species. The structural similarity of retinoic acid (RA), 4-HPR, and α-tocopherol (vitamin E) led us to investigate whether 4-HPR exhibits antioxidant activity. It was found that 4-HPR scavenged α, α-diphenyl-β-picrylhydrazyl (DPPH) radicals in a 1 : 1 ratio in contrast to vitamin E, where a 1 : 2 ratio relative to DPPH radicals was observed. In addition, linoleic acid peroxidation initiated by hydroxyl radaicals was decreased by 4-HPR to the same extent as by vitamin E. Furthermore, lipid peroxidation in rat liver microsomes was reduced by 4-HPR to a greater extent than by vitamin E. Based on these results, 4-HPR appears to be an effective antioxidant that may have clinical utility for diseases treated with vitamin E.