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-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-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-kappa B 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.
Murakami
Akira
A
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Iwade-Uchita, Wakayama 649-6493, Japan. murakami@bio.waka.kindai.ac.jp
Nakamura
Yoshimasa
Y
Koshimizu
Koichi
K
Takahashi
Daisuke
D
Matsumoto
Kazuhiro
K
Hagihara
Kazuma
K
Taniguchi
Hisaji
H
Nomura
Eisaku
E
Hosoda
Asao
A
Tsuno
Takuo
T
Maruta
Yuko
Y
Kim
Ha Won
HW
Kawabata
Kyuichi
K
Ohigashi
Hajime
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D003373:Coumaric Acids / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D020672:I-kappa B Proteins; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D000072000:NF-KappaB Inhibitor alpha; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D010212:Papilloma / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases; D012878:Skin Neoplasms / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C464609:2-methyl-1-butyl ferulic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D003373:Coumaric Acids; D004268:DNA-Binding Proteins; D020672:I-kappa B Proteins; D007527:Isoenzymes; C000606205:Nfkbia protein, mouse; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C004999:ferulic acid; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases