TY - JOUR
T1 - The potent anti-tumor-promoting agent isoliquiritigenin
AU - Yamamoto, Satoshi
AU - Aizu, Eriko
AU - Jiang, Hong
AU - Nakadate, Teruo
AU - Kiyoto, Itsumi
AU - Wang, Jian Chun
AU - Kato, Ryuichi
N1 - Funding Information:
We thank Mr Takaki Kaenyama and Miss Chino Otsuka for their competent technical assistance. This study was supported in part by grants from the Ministry of Education, Science and Culture of Japan, a grant from Takeda Science Foundation, Osaka, Japan, and a grant from the Sagawa Foundation for Promotion of Cancer Research. The work was also supported by a grant from Keio-Gijuku Academic Development Funds, Keio University, and a grant from the Health-consulting Center, School of Medicine, Keio University, Tokyo, Japan.
PY - 1991/2
Y1 - 1991/2
N2 - A topical application of a chalcone derivative, 4,2',4'- trihydroxychalcone (isoliquirtigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigenin potently inhibited 7,12-dimethyl- benz[a]anthracene (DMBA)-initiated and TPA-promoted skin papilloma formation. This inhibitory effect of isoliquiritigenin was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. Isoliquiritigenin also inhibited epidermal ODC induction and skin tumor promotion caused by 7-bromomethylbenz[a]anthracene (BrMBA), a non-TPA type of tumor-promoting agent, in DMBA initiated mice. Isoliquiritigenin inhibits neither 12-lipoxy- genase nor cyclooxygenase in epidermal subeellular fractioos. This compound, however, inhibited TPA-stimulated prostaglandin E2 (PGE2) production in intact epidermal cells. ODC induction caused by TPA was inhibited by a topical application of cyclooxygenase inhibitor, indomethacin. Inhibition of ODC induction by Indomethacin was counteracted by a topical application of PGE2 while inhibition caused by isoliquiritigenin was not overcome by PGE2 The results suggest that a mechanism other than the inhibition of PGE2 production is involved in the anti-tumor- promoting action of isoliquiritigenin. Isoliquiritigenin failed to inhibit phospholipase A2 activity of platelet sonicates, but inhibited platelet 12-lipoxygenase and 5-lipoxygenase in polymorphonuclear leukocytes. Therefore, it might be possible that isoliquiritigenin exerts its anti-tumor-promoting action through the lipoxygenase inhibition by acting on cells other than the target epidermal cells. Our present results, in combination with our previous data, demonstrate that some chalcone derivatives and flavonoids which show a potent lipoxygenase inhibitory action act on a common step in the skin tumorpromotion caused by two different types of tumor- promoting agents, i.e. TPA and BrMBA, and suggest that these compounds show promise as drugs to prevent tumor promotion.
AB - A topical application of a chalcone derivative, 4,2',4'- trihydroxychalcone (isoliquirtigenin) inhibited epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. inflammation, caused by a topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) in CD-1 mice. In addition, isoliquiritigenin potently inhibited 7,12-dimethyl- benz[a]anthracene (DMBA)-initiated and TPA-promoted skin papilloma formation. This inhibitory effect of isoliquiritigenin was not due to any damage inflicted on the initiated cells but due to its anti-tumor-promoting action. Isoliquiritigenin also inhibited epidermal ODC induction and skin tumor promotion caused by 7-bromomethylbenz[a]anthracene (BrMBA), a non-TPA type of tumor-promoting agent, in DMBA initiated mice. Isoliquiritigenin inhibits neither 12-lipoxy- genase nor cyclooxygenase in epidermal subeellular fractioos. This compound, however, inhibited TPA-stimulated prostaglandin E2 (PGE2) production in intact epidermal cells. ODC induction caused by TPA was inhibited by a topical application of cyclooxygenase inhibitor, indomethacin. Inhibition of ODC induction by Indomethacin was counteracted by a topical application of PGE2 while inhibition caused by isoliquiritigenin was not overcome by PGE2 The results suggest that a mechanism other than the inhibition of PGE2 production is involved in the anti-tumor- promoting action of isoliquiritigenin. Isoliquiritigenin failed to inhibit phospholipase A2 activity of platelet sonicates, but inhibited platelet 12-lipoxygenase and 5-lipoxygenase in polymorphonuclear leukocytes. Therefore, it might be possible that isoliquiritigenin exerts its anti-tumor-promoting action through the lipoxygenase inhibition by acting on cells other than the target epidermal cells. Our present results, in combination with our previous data, demonstrate that some chalcone derivatives and flavonoids which show a potent lipoxygenase inhibitory action act on a common step in the skin tumorpromotion caused by two different types of tumor- promoting agents, i.e. TPA and BrMBA, and suggest that these compounds show promise as drugs to prevent tumor promotion.
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U2 - 10.1093/carcin/12.2.317
DO - 10.1093/carcin/12.2.317
M3 - Article
C2 - 1899810
AN - SCOPUS:0026070546
SN - 0143-3334
VL - 12
SP - 317
EP - 323
JO - Carcinogenesis
JF - Carcinogenesis
IS - 2
ER -
