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

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

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% (P2-test) and 42% (P2- 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
Volume140
Issue number1-2
DOIs
Publication statusPublished - Jun 1 1999
Externally publishedYes

Fingerprint

Ephrin-A5
Artemisia
Epoxy Compounds
Tetradecanoylphorbol Acetate
Ether
Oxidative Stress
Neoplasms
Inbred ICR Mouse
Skin
Carcinogens
Carcinogenesis
Virus Activation
Curcuma
9,10-Dimethyl-1,2-benzanthracene
Curcumin
HL-60 Cells
Peroxides
spiroketal
Human Herpesvirus 4
Inhibitory Concentration 50

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

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

In: Cancer Letters, Vol. 140, No. 1-2, 01.06.1999, p. 37-45.

Research output: Contribution to journalArticle

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abstract = "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{\%} (P2-test) and 42{\%} (P2- generation is an effective chemopreventer of mouse skin carcinogenesis by their antioxidative property. Copyright (C) 1999 Elsevier Science Ireland Ltd.",
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