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

• Published in: Cancer letters 2002-06, Vol.180 (2), p.121-129
• Main Authors: Murakami, Akira, Nakamura, Yoshimasa, Koshimizu, Koichi, Takahashi, Daisuke, Matsumoto, Kazuhiro, Hagihara, Kazuma, Taniguchi, Hisaji, Nomura, Eisaku, Hosoda, Asao, Tsuno, Takuo, Maruta, Yuko, Kim, Ha Won, Kawabata, Kyuichi, Ohigashi, Hajime
• Format: Article
• Language: English
• Subjects: Acids; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anticarcinogenic Agents - pharmacology; Biological and medical sciences; Biotechnology; Carcinogenesis, carcinogens and anticarcinogens; Chemical agents; Coumaric Acids - pharmacology; Cyclooxygenase 2; Disease prevention; DNA-Binding Proteins - metabolism; Enzymes; Experiments; Female; Free radicals; I-kappa B Proteins; I-κB; Inducible nitric oxide synthase; Isoenzymes - antagonists & inhibitors; Kinases; Medical sciences; Mice; Mice, Inbred ICR; NF-KappaB Inhibitor alpha; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase Type II; Oxidative Stress; Papilloma - prevention & control; Phosphorylation; Prostaglandin-Endoperoxide Synthases; Proteins; Rodents; Science; Skin; Skin Neoplasms - prevention & control; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(01)00858-8

In our previous study, FA15 (2-methyl-1-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-γ-induced protein expressions of inducible nitric oxide synthase and cyclooxygenase-2, and also inhibited the release of tumor necrosis factor-α accompanied by suppression of I-κB 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 from natural sources, is a novel chemopreventive agent, both structurally and functionally.