FA15, a hydrophobic derivative of ferulic acid, suppresses inflammatory responses and skin tumor promotion: comparison with ferulic acid

In our previous study. FA15 (2-methyl-I-butyl ferulic acid) was chemically synthesized as a novel ferulic acid (FA) analog, and found to notably suppress phorbol ester-induced Epstein-Barr virus activation and superoxide anion generation in vitro. In this report, we demonstrated that FA15 in contrast to FA, markedly Suppressed the combined lipopolysaccharide and interferon-gamma-induced protein expressions of inducible nitric oxide synthase and cyclooxygenase-2, and also inhibited the release of tumor necrosis factor-alpha accompanied by suppression of I-kappaB degradation in RAW264.7, a murine macrophage cell line. In ICR mouse skin, topical application of FA15 significantly attenuated phorbol ester-triggered hydrogen peroxide production and edema formation as well as papilloma development while that of FA did not. Our results suggest that FA15, derived front natural sources. is a novel chemopreventive agent, both structurally and functionally. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.