The potent anti-tumor-promoting agent isoliquiritigenin

Satoshi Yamamoto, Eriko Yokota, Hong Jiang, Teruo Nakadate, Itsumi Kiyoto, Jian Chun Wang, Ryuichi Kato

Research output: Contribution to journalArticle

114 Citations (Scopus)

Abstract

A topical application of a chalcone derivative, 4,2′,4′-trihydroxychalcone (isoliquiritigenin) 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-dimethylbenz[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-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. 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 tumor promotion 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.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalCarcinogenesis
Volume12
Issue number2
Publication statusPublished - 1991 Feb

Fingerprint

Tumors
Tumor
Prostaglandins
Tetradecanoylphorbol Acetate
Ornithine Decarboxylase
Dinoprostone
Neoplasms
Proof by induction
Skin
Arachidonate 12-Lipoxygenase
Platelets
Chalcone
Anthracene
9,10-Dimethyl-1,2-benzanthracene
Cell
Lipoxygenase
Mouse
Indomethacin
Blood Platelets
Derivatives

ASJC Scopus subject areas

  • Cancer Research
  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Physiology (medical)
  • Physiology
  • Behavioral Neuroscience

Cite this

Yamamoto, S., Yokota, E., Jiang, H., Nakadate, T., Kiyoto, I., Wang, J. C., & Kato, R. (1991). The potent anti-tumor-promoting agent isoliquiritigenin. Carcinogenesis, 12(2), 317-323.

The potent anti-tumor-promoting agent isoliquiritigenin. / Yamamoto, Satoshi; Yokota, Eriko; Jiang, Hong; Nakadate, Teruo; Kiyoto, Itsumi; Wang, Jian Chun; Kato, Ryuichi.

In: Carcinogenesis, Vol. 12, No. 2, 02.1991, p. 317-323.

Research output: Contribution to journalArticle

Yamamoto, S, Yokota, E, Jiang, H, Nakadate, T, Kiyoto, I, Wang, JC & Kato, R 1991, 'The potent anti-tumor-promoting agent isoliquiritigenin', Carcinogenesis, vol. 12, no. 2, pp. 317-323.
Yamamoto S, Yokota E, Jiang H, Nakadate T, Kiyoto I, Wang JC et al. The potent anti-tumor-promoting agent isoliquiritigenin. Carcinogenesis. 1991 Feb;12(2):317-323.
Yamamoto, Satoshi ; Yokota, Eriko ; Jiang, Hong ; Nakadate, Teruo ; Kiyoto, Itsumi ; Wang, Jian Chun ; Kato, Ryuichi. / The potent anti-tumor-promoting agent isoliquiritigenin. In: Carcinogenesis. 1991 ; Vol. 12, No. 2. pp. 317-323.
@article{cdae781ebf5b4e5a8d0b805a029d52ee,
title = "The potent anti-tumor-promoting agent isoliquiritigenin",
abstract = "A topical application of a chalcone derivative, 4,2′,4′-trihydroxychalcone (isoliquiritigenin) 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-dimethylbenz[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-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. 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 tumor promotion 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.",
author = "Satoshi Yamamoto and Eriko Yokota and Hong Jiang and Teruo Nakadate and Itsumi Kiyoto and Wang, {Jian Chun} and Ryuichi Kato",
year = "1991",
month = "2",
language = "English",
volume = "12",
pages = "317--323",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - The potent anti-tumor-promoting agent isoliquiritigenin

AU - Yamamoto, Satoshi

AU - Yokota, Eriko

AU - Jiang, Hong

AU - Nakadate, Teruo

AU - Kiyoto, Itsumi

AU - Wang, Jian Chun

AU - Kato, Ryuichi

PY - 1991/2

Y1 - 1991/2

N2 - A topical application of a chalcone derivative, 4,2′,4′-trihydroxychalcone (isoliquiritigenin) 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-dimethylbenz[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-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. 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 tumor promotion 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 (isoliquiritigenin) 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-dimethylbenz[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-lipoxygenase nor cyclooxygenase in epidermal subcellular fractions. 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 tumor promotion 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.

UR - http://www.scopus.com/inward/record.url?scp=0026070546&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026070546&partnerID=8YFLogxK

M3 - Article

C2 - 1899810

AN - SCOPUS:0026070546

VL - 12

SP - 317

EP - 323

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 2

ER -