Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling.
Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3152552?pdf=render |
| _version_ | 1811231782401474560 |
|---|---|
| author | Xiangsheng Xiao Dingbo Shi Liqun Liu Jingshu Wang Xiaoming Xie Tiebang Kang Wuguo Deng |
| author_facet | Xiangsheng Xiao Dingbo Shi Liqun Liu Jingshu Wang Xiaoming Xie Tiebang Kang Wuguo Deng |
| author_sort | Xiangsheng Xiao |
| collection | DOAJ |
| description | Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers. |
| first_indexed | 2024-04-12T10:50:52Z |
| format | Article |
| id | doaj.art-3dcd2595a0e24a68aac2f9c905307191 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T10:50:52Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3dcd2595a0e24a68aac2f9c9053071912022-12-22T03:36:14ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0168e2293410.1371/journal.pone.0022934Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling.Xiangsheng XiaoDingbo ShiLiqun LiuJingshu WangXiaoming XieTiebang KangWuguo DengQuercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2), an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG) E(2) production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT) activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.http://europepmc.org/articles/PMC3152552?pdf=render |
| spellingShingle | Xiangsheng Xiao Dingbo Shi Liqun Liu Jingshu Wang Xiaoming Xie Tiebang Kang Wuguo Deng Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. PLoS ONE |
| title | Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. |
| title_full | Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. |
| title_fullStr | Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. |
| title_full_unstemmed | Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. |
| title_short | Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling. |
| title_sort | quercetin suppresses cyclooxygenase 2 expression and angiogenesis through inactivation of p300 signaling |
| url | http://europepmc.org/articles/PMC3152552?pdf=render |
| work_keys_str_mv | AT xiangshengxiao quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT dingboshi quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT liqunliu quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT jingshuwang quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT xiaomingxie quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT tiebangkang quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling AT wuguodeng quercetinsuppressescyclooxygenase2expressionandangiogenesisthroughinactivationofp300signaling |