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.

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 microM), 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 micromol) 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 chi2-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.

• Authors: Y Nakamura, N Kawamoto, Y Ohto, K Torikai, A Murakami, H Ohigashi
• Journal: Cancer letters (Cancer Lett) Vol. 140 Issue 1-2 Pg. 37-45 (Jun 01 1999) ISSN: 0304-3835 [Print] Ireland
• PMID: 10403539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Al 1 spiroketal enol ether epoxide
• Anticarcinogenic Agents
• Antineoplastic Agents, Phytogenic
• Pyrans
• Spiro Compounds
• 9,10-Dimethyl-1,2-benzanthracene
• Hydrogen Peroxide
• Tetradecanoylphorbol Acetate

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Anticarcinogenic Agents (pharmacology, therapeutic use)
• Antineoplastic Agents, Phytogenic (pharmacology, therapeutic use)
• Carcinogenicity Tests
• Dose-Response Relationship, Drug
• Epidermis (drug effects, metabolism)
• Female
• HL-60 Cells
• Herpesvirus 4, Human (metabolism)
• Humans
• Hydrogen Peroxide (metabolism)
• Intracellular Fluid (drug effects, metabolism)
• Mice
• Mice, Inbred ICR
• Oxidative Stress (drug effects)
• Pyrans (pharmacology, therapeutic use)
• Skin Neoplasms (chemically induced, prevention & control)
• Spiro Compounds (pharmacology, therapeutic use)
• Tetradecanoylphorbol Acetate
• Tumor Cells, Cultured
• Virus Activation (drug effects)