Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice

Min Hsiung Pan, Ching Shu Lai, Ying Jan Wang, Chi Tang Ho

研究成果: Article

102 引文 (Scopus)

摘要

Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. In this study, we investigated the inhibitory effects of acacetin and a related compound, wogonin, on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells activated with lipopolysaccharide (LPS). Acacetin markedly and actively inhibited the transcriptional activation of iNOS and COX-2. Western blotting, reverse transcription-polymerase chain reaction (PCR), and real-time PCR analyses demonstrated that acacetin significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-inducted macrophages. Treatment with acacetin reduced translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB. The activation of NFκB was inhibited by prevention of the degradation of inhibitor κB (IκB). Furthermore, acacetin inhibited LPS-induced phosphorylation as well as degradation of IκBα. We further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-induced macrophages. We found that acacetin also inhibited LPS-induced activation of PI3K/Akt and p44/42, but not p38 MAPK. After initiation of 7,12-dimethlybene[a]anthracene (DMBA), applying acacentin topically before each 12-O-tetradecanoylphorbol 13-acetat (TPA) treatment was found to reduce the number of papillomas at 20 weeks. Taken together, these results show that acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.

原文English
頁(從 - 到)1293-1303
頁數11
期刊Biochemical Pharmacology
72
發行號10
DOIs
出版狀態Published - 2006 十一月 15

指紋

Macrophages
Lipopolysaccharides
Tumors
Neoplasms
Chemical activation
1-Phosphatidylinositol 4-Kinase
Phosphotransferases
Polymerase chain reaction
Corrosion inhibitors
Mitogen-Activated Protein Kinases
acacetin
Degradation
9,10-Dimethyl-1,2-benzanthracene
Phosphorylation
Macrophage Activation
Papilloma
p38 Mitogen-Activated Protein Kinases
Transcription
Flavonoids
Gene expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology

引用此文

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title = "Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice",
abstract = "Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. In this study, we investigated the inhibitory effects of acacetin and a related compound, wogonin, on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells activated with lipopolysaccharide (LPS). Acacetin markedly and actively inhibited the transcriptional activation of iNOS and COX-2. Western blotting, reverse transcription-polymerase chain reaction (PCR), and real-time PCR analyses demonstrated that acacetin significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-inducted macrophages. Treatment with acacetin reduced translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB. The activation of NFκB was inhibited by prevention of the degradation of inhibitor κB (IκB). Furthermore, acacetin inhibited LPS-induced phosphorylation as well as degradation of IκBα. We further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-induced macrophages. We found that acacetin also inhibited LPS-induced activation of PI3K/Akt and p44/42, but not p38 MAPK. After initiation of 7,12-dimethlybene[a]anthracene (DMBA), applying acacentin topically before each 12-O-tetradecanoylphorbol 13-acetat (TPA) treatment was found to reduce the number of papillomas at 20 weeks. Taken together, these results show that acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.",
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Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice. / Pan, Min Hsiung; Lai, Ching Shu; Wang, Ying Jan; Ho, Chi Tang.

於: Biochemical Pharmacology, 卷 72, 編號 10, 15.11.2006, p. 1293-1303.

研究成果: Article

TY - JOUR

T1 - Acacetin suppressed LPS-induced up-expression of iNOS and COX-2 in murine macrophages and TPA-induced tumor promotion in mice

AU - Pan, Min Hsiung

AU - Lai, Ching Shu

AU - Wang, Ying Jan

AU - Ho, Chi Tang

PY - 2006/11/15

Y1 - 2006/11/15

N2 - Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. In this study, we investigated the inhibitory effects of acacetin and a related compound, wogonin, on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells activated with lipopolysaccharide (LPS). Acacetin markedly and actively inhibited the transcriptional activation of iNOS and COX-2. Western blotting, reverse transcription-polymerase chain reaction (PCR), and real-time PCR analyses demonstrated that acacetin significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-inducted macrophages. Treatment with acacetin reduced translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB. The activation of NFκB was inhibited by prevention of the degradation of inhibitor κB (IκB). Furthermore, acacetin inhibited LPS-induced phosphorylation as well as degradation of IκBα. We further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-induced macrophages. We found that acacetin also inhibited LPS-induced activation of PI3K/Akt and p44/42, but not p38 MAPK. After initiation of 7,12-dimethlybene[a]anthracene (DMBA), applying acacentin topically before each 12-O-tetradecanoylphorbol 13-acetat (TPA) treatment was found to reduce the number of papillomas at 20 weeks. Taken together, these results show that acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.

AB - Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. In this study, we investigated the inhibitory effects of acacetin and a related compound, wogonin, on the induction of NO synthase (NOS) and COX-2 in RAW 264.7 cells activated with lipopolysaccharide (LPS). Acacetin markedly and actively inhibited the transcriptional activation of iNOS and COX-2. Western blotting, reverse transcription-polymerase chain reaction (PCR), and real-time PCR analyses demonstrated that acacetin significantly blocked protein and mRNA expression of iNOS and COX-2 in LPS-inducted macrophages. Treatment with acacetin reduced translocation of nuclear factor-κB (NFκB) subunit and the dependent transcriptional activity of NFκB. The activation of NFκB was inhibited by prevention of the degradation of inhibitor κB (IκB). Furthermore, acacetin inhibited LPS-induced phosphorylation as well as degradation of IκBα. We further investigated the roles of tyrosine kinase, phosphatidylinositiol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) in LPS-induced macrophages. We found that acacetin also inhibited LPS-induced activation of PI3K/Akt and p44/42, but not p38 MAPK. After initiation of 7,12-dimethlybene[a]anthracene (DMBA), applying acacentin topically before each 12-O-tetradecanoylphorbol 13-acetat (TPA) treatment was found to reduce the number of papillomas at 20 weeks. Taken together, these results show that acacetin down regulates inflammatory iNOS and COX-2 gene expression in macrophages by inhibiting the activation of NFκB by interfering with the activation PI3K/Akt/IKK and MAPK, suggesting that acacetin is a functionally novel agent capable of preventing inflammation-associated tumorigenesis.

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