Download PDF
Planta Med 2005; 71(1): 84-87
DOI: 10.1055/s-2005-837758
Letter
© Georg Thieme Verlag KG Stuttgart · New York

Antitumor-Promoting Activity of Coumarins from Citrus Plants

Chihiro Ito1 , Masataka Itoigawa2 , Motoharu Ju-ichi3 , Naoyuki Sakamoto4 , Harukuni Tokuda4 , Hoyoku Nishino4 , Hiroshi Furukawa1
  • 1Faculty of Pharmacy, Meijo University, Tempaku, Nagoya, Japan
  • 2Tokai Gakuen University, Tempaku, Nagoya, Japan
  • 3Faculty of Pharmaceutical Sciences, Mukogawa Women’s University, Nishinomiya, Hyogo, Japan
  • 4Department of Molecular Biochemistry, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, Japan
Further Information

Publication History

Received: April 8, 2004

Accepted: June 4, 2004

Publication Date:
27 January 2005 (online)

Also available at
    Permissions and Reprints

Abstract

In order to identify antitumor-promoting agents, we performed primary in vitro screening of 31 coumarins isolated from 11 plants of the Citrus species (Rutaceae), examining their possible inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Some of the 8-substituted coumarins, 8-formyl-7-hydroxycoumarin (5), osthenol (7), demethylauraptenol (8), osthenon (9) and dihydroosthenon (10), were found to significantly inhibit EBV-EA activation (IC50 : 129 - 207 mol ratio/32 pmol TPA). Osthenol (7) exhibited a marked inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

References

  • 1 Ito C, Matsuoka M, Oka T, Ju-ichi M, Niwa M, Omura M, Furukawa H. New binary coumarins from Citrus plants.  Chemical & Pharmaceutical Bulletin.. 1990;  38 1230-2
    PubMedSearch in Google Scholar
  • 2 Ito C, Fujiwara K, Kajita M, Ju-ichi M, Takemura Y, Suzuki Y. et al . New coumarins from Citrus plants.  Chemical & Pharmaceutical Bulletin.. 1991;  39 2509-13
    PubMedSearch in Google Scholar
  • 3 Takemura Y, Kawaguchi H, Maki S, Ju-ichi M, Omura M, Ito C, Furukawa H. Studies on the constituents of Yalaha. Structures of a new acridone alkaloid and two new coumarins.  Chemical & Pharmaceutical Bulletin. 1996;  44 804-9
    PubMedSearch in Google Scholar
  • 4 Kan W S. Manual of Medicinal Plants in Taiwan Vol 25. National Research Institute of Chinese Medicine Taiwan; 1972: pp 77-8 and 359 - 72
    Search in Google Scholar
  • 5 Iwase Y, Takemura Y, Ju-ichi M, Kawaii S, Yano M, Okuda Y. et al . Inhibitory effect of Epstein-Barr virus activation by Citrus fruits, a cancer chemopreventor.  Cancer Letters.. 1999;  139 227-36
    CrossrefPubMedSearch in Google Scholar
  • 6 Ito C, Itoigawa M, Furukawa H, Tokuda H, Okuda Y, Mukainaka T. et al . Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus activation assay.  Cancer Letters. 1999;  138 87-92
    CrossrefPubMedSearch in Google Scholar
  • 7 Murakami A, Kuki W, Takahashi Y, Yonei H, Nakamura Y, Ohto Y. et al . Auraptene, a Citrus coumarin, inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in ICR mouse skin, possibly through suppression of superoxide generation in leukocytes.  Japanese Journal of Cancer Research. 1997;  88 443-52
    PubMedSearch in Google Scholar
  • 8 Iwase Y, Takemura Y, Ju-ichi M, Ito C, Furukawa H, Kawaii S. et al . Inhibitory effect of flavonoids from Citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.  Cancer Letters. 2000;  154 101-5
    CrossrefPubMedSearch in Google Scholar
  • 9 Iwase Y, Takemura Y, Ju-ichi M, Yano M, Ito C, Furukawa H. et al . Cancer chemopreventive activity of 3,5,6,7,8,3′,4′-heptamethoxyflavone from the peel of Citrus plants.  Cancer Letters. 2001;  163 7-9
    CrossrefPubMedSearch in Google Scholar
  • 10 Takemura Y, Ju-ichi M, Ito C, Furukawa H, Tokuda H. Studies on the inhibitory effects of some acridone alkaloids on Epstein-Barr virus activation.  Planta Medica. 1995;  61 366-8
    PubMedSearch in Google Scholar
  • 11 Itoigawa M, Ito C, Wu T -S, Enjo F, Tokuda H, Nishino H. et al . Cancer chemopreventive activity of acridone alkaloids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.  Cancer Letters. 2003;  193 133-8
    CrossrefPubMedSearch in Google Scholar
  • 12 Murakami A, Ohigashi H, Koshimizu K. Anti-tumor promotion with food phytochemicals: A strategy for cancer chemoprevention.  Bioscience Biotechnology and Biochemistry. 1996;  60 1-8
    PubMedSearch in Google Scholar
  • 13 T sushima M, Maoka T, Katsuyama M, Kozuka M, Matsuno T, Tokuda H. et al . Inhibitory effect of natural carotenoids on Epstein-Barr virus activation activity of a tumor promoter in Raji cells. A screening study for anti-tumor promoters.  Biological & Pharmaceutical Bulletin.. 1995;  18 227-33
    PubMedSearch in Google Scholar
  • 14 Huang M T, Ma W, Lu Y P, Chang R L, Fisher C, Manchand P S. et al . Effects of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin on 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion.  Carcinogenesis. 1995;  16 2493-7
    PubMedSearch in Google Scholar
  • 15 Ishida J, Kozuka M, Wang H, Konoshima T, Tokuda H, Okuda M. et al . Antitumor-promoting effects of cyclic diarylheptanoids on Epstein-Barr virus activation and two-stage mouse skin carcinogenesis.  Cancer Letters. 2000;  159 135-40
    CrossrefPubMedSearch in Google Scholar

Prof. Masataka Itoigawa

Tokai Gakuen University

2-901 Nakahira

Tempaku-ku

Nagoya, 468-8514

Japan

Phone: +81-52-801-1201

Fax: +81-52-804-1044

Email: itoigawa@tokaigakuen-c.ac.jp