Auraptene, an Alkyloxylated Coumarin from Citrus natsudaidai HAYATA, Inhibits Mouse Skin Tumor Promotion and Rat Colonie Aberrant Crypt Foci Formation

Akira Murakami, Wataru Kuki, Yasuo Takahashi, Hiroshi Yonei, Takuji Tanaka, Hiroki Makita, Keiji Wada, Naomi Ueda, Masanobu Haga, Yoshimasa Nakamura, Yoshimi Ohto, Oe Kyung Kim, Hajime Ohigashi, Koichi Koshimizu

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Auraptene, a coumarin-related compound, has been isolated from the cold-pressed oil of natsumikan (Citrus natsudaidai HAYATA), as an inhibitor of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus (EBV) activation in Raji cells. In a two-stage carcinogenesis experiment with 1.6 nmol of TPA and 0.19 μmol of 7,12-dimethyl benz[a]anthracene (DMBA) in ICR mouse skin, topical application of 160 nmol of auraptene significantly reduced tumor incidence and the number of tumors per mouse by 27% and 23%, respectively. Auraptene at 50 μM almost completely suppressed TPA-induced superoxide (O2-)and hydroperoxide (ROOH) generation in differentiated HL-60 cells as well as lypopolysaccharide (LPS)/interferon-γ(IFN-γ)-induced nitric oxide (NO) generation in RAW 264.7 cells. Dietary feeding of auraptene at a dose of 100 or 500 ppm inhibited azoxymethane (AOM)-induced rat colonic aberrant crypt foci (ACF) formation in a dose-dependent manner. Oral administration of auraptene (50 - 200 mg/kg body wt.) clearly enhanced the glutathione S-transferase (GST) activity in mouse liver, suggesting that auraptene is an effective chemopreventer in both tumor initiation and promotion phases.

Original languageEnglish
Pages (from-to)86-95
Number of pages10
JournalACS Symposium Series
Volume701
Publication statusPublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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