A diacetylenic spiroketal enol ether epoxide, AL-1, from Artemisia lactiflora inhibits 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion possibly by suppression of oxidative stress

Yoshimasa Nakamura, Norihiko Kawamoto, Yoshimi Ohto, Koji Torikai, Akira Murakami, Hajime Ohigashi

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The inhibitory effects of the diacetylenic spiroketal enol ether epoxide AL-1 from Artemisia lactiflora on a variety of tumor promoter-induced biological responses such as oxidative stress as well as tumor promotion in ICR mouse skin were investigated. AL-1 inhibited TPA-induced intracellular peroxide formation in differentiated HL-60 cells, suggesting that this suppression might be attributable to the inhibition of O2- generation. In a double TPA application system in mouse skin, double pretreatments of AL-1 (810 nmol) significantly suppressed double TPA application-induced H2O2 generation. Pretreatment of AL-1 only before the second TPA treatment was sufficient to inhibit, while only with first treatment was not. From these results we concluded that AL-1 is a specific inhibitor of the activation phase in H2O2 production induced by double TPA treatments. In addition, AL-1 strongly inhibited tumor promoter-induced Epstein-Barr virus (EBV) activation in Raji cells (IC50=0.5 μM), which was comparable to or even stronger than that of curcumin, a well-known antioxidative chemopreventer from turmeric. In a two-stage carcinogenesis experiment with TPA (topical application at 1.6 nmol) and 7,12-dimethylbenz[a]anthracene (DMBA, at 0.19 μmol) in ICR mouse skin, topical application of AL-1 (at 160 nmol) significantly reduced tumor incidence, the numbers of tumors per mouse, and edema formation by 58% (P<0.01 in t-test), 20% (P<0.005 in χ2-test) and 42% (P<0.01), respectively. These results together indicate that an inhibitor of O2- generation is an effective chemopreventer of mouse skin carcinogenesis by their antioxidative property. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalCancer Letters
Issue number1-2
Publication statusPublished - Jun 1 1999



  • Artemisia lactiflora
  • Cancer chemoprevention
  • Diacetylene spiroketal enol ether
  • Mouse skin
  • Superoxide

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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