Inhibitory effect of garcinol against 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice

Wei Lun Hung, Chi Mei Liu, Ching Shu Lai, Chi Tang Ho, Min Hsiung Pan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Garcinol, a polyisoprenylated benzophenone derivative, is one of the major constituents isolated from the Garcinia indica fruit rind. Previous studies have reported that garcinol exhibits many biological benefits, including anti-oxidative, anti-inflammatory, and anti-tumour activities both in vitro and in vivo. However, little is known about the garcinol-mediated protection from inflammation-associated skin tumorigenesis. The aim of this study is to evaluate the inhibitory effects of garcinol against 12-. O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin inflammation and tumour promotion. Topical pre-treatment of mouse skin with garcinol significantly reduced TPA-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Pre-treatment with garcinol on mouse skin also suppressed the TPA-induced nuclear translocation of nuclear factor-κB (NF-κB) and its subsequent DNA binding by blocking phosphorylation of inhibitor κB α (IκBα) and the p65 subunit leading to the degradation of IκBα. Moreover, garcinol markedly reduced TPA-induced activation of extracellular signal-regulated kinases (ERK), c-Jun-N-terminal kinases (JNK), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt, which are upstream of NF-κB. Finally, topical application of garcinol significantly attenuated 7, 12-dimethylbenz[α]anthracene (DMBA)/TPA-induced mouse skin tumour promotion by reducing tumour incidence and papilloma tumour size at 18 weeks following treatment. Based on these findings, our data suggest that garcinol may serve as a potent chemopreventive agent capable of inhibiting inflammation-associated skin tumorigenesis.

Original languageEnglish
Article number1250
Pages (from-to)432-444
Number of pages13
JournalJournal of Functional Foods
Volume18
DOIs
Publication statusPublished - Jan 1 2015
Externally publishedYes

Fingerprint

Tetradecanoylphorbol Acetate
skin (animal)
carcinogenesis
Carcinogenesis
inflammation
acetates
Inflammation
Skin
mitogen-activated protein kinase
mice
neoplasms
pretreatment
benzophenone
fruit peels
papilloma
Neoplasms
topical application
phosphatidylinositol 3-kinase
prostaglandin synthase
Garcinia

Keywords

  • 12-O-tetradecanoylphorbol 13-acetate
  • Chemoprevention
  • Garcinol
  • Inflammation
  • Skin cancer

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science
  • Nutrition and Dietetics

Cite this

Inhibitory effect of garcinol against 12-O-tetradecanoylphorbol 13-acetate-induced skin inflammation and tumorigenesis in mice. / Hung, Wei Lun; Liu, Chi Mei; Lai, Ching Shu; Ho, Chi Tang; Pan, Min Hsiung.

In: Journal of Functional Foods, Vol. 18, 1250, 01.01.2015, p. 432-444.

Research output: Contribution to journalArticle

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abstract = "Garcinol, a polyisoprenylated benzophenone derivative, is one of the major constituents isolated from the Garcinia indica fruit rind. Previous studies have reported that garcinol exhibits many biological benefits, including anti-oxidative, anti-inflammatory, and anti-tumour activities both in vitro and in vivo. However, little is known about the garcinol-mediated protection from inflammation-associated skin tumorigenesis. The aim of this study is to evaluate the inhibitory effects of garcinol against 12-. O-tetradecanoylphorbol 13-acetate (TPA)-induced mouse skin inflammation and tumour promotion. Topical pre-treatment of mouse skin with garcinol significantly reduced TPA-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Pre-treatment with garcinol on mouse skin also suppressed the TPA-induced nuclear translocation of nuclear factor-κB (NF-κB) and its subsequent DNA binding by blocking phosphorylation of inhibitor κB α (IκBα) and the p65 subunit leading to the degradation of IκBα. Moreover, garcinol markedly reduced TPA-induced activation of extracellular signal-regulated kinases (ERK), c-Jun-N-terminal kinases (JNK), p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K)/Akt, which are upstream of NF-κB. Finally, topical application of garcinol significantly attenuated 7, 12-dimethylbenz[α]anthracene (DMBA)/TPA-induced mouse skin tumour promotion by reducing tumour incidence and papilloma tumour size at 18 weeks following treatment. Based on these findings, our data suggest that garcinol may serve as a potent chemopreventive agent capable of inhibiting inflammation-associated skin tumorigenesis.",
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AU - Ho, Chi Tang

AU - Pan, Min Hsiung

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