Anti‐Metastatic Effect of Supercritical Extracts from the Citrus hassaku Pericarp via Inhibition of C‐X‐C Chemokine Receptor Type 4 (CXCR4) and Matrix Metalloproteinase‐9 (MMP‐9)
Identifieur interne : 001083 ( Main/Exploration ); précédent : 001082; suivant : 001084Anti‐Metastatic Effect of Supercritical Extracts from the Citrus hassaku Pericarp via Inhibition of C‐X‐C Chemokine Receptor Type 4 (CXCR4) and Matrix Metalloproteinase‐9 (MMP‐9)
Auteurs : Chulwon Kim [Corée du Sud] ; Dongmin Kim [Corée du Sud] ; Dongwoo Nam [Corée du Sud] ; Won-Seok Chung [Corée du Sud] ; Kyoo Seok Ahn [Corée du Sud] ; Sung-Hoon Kim [Corée du Sud] ; Seung-Hoon Choi [Corée du Sud] ; Bum Sang Shim [Corée du Sud] ; Somi K. Cho [Corée du Sud] ; Kwang Seok Ahn [Corée du Sud]Source :
- Phytotherapy Research [ 0951-418X ] ; 2014-09.
Abstract
The fruit of hassaku (Citrus hassaku Hort. ex Tanaka) is locally known as phalsak in Korea. Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB‐induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA‐MB‐231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase‐9 (MMP‐9) expression and its enzymatic activity under non‐cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS‐induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF‐κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12‐stimulated invasion of MDA‐MB‐231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP‐9 expressions through blockade of NF‐κB activation and thus has the potential to suppress metastasis of breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.
Url:
DOI: 10.1002/ptr.5140
Affiliations:
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Recently, the fruit extract has been known to exhibit in vivo preventive effects against UVB‐induced pigmentation, antiallergic activity, and enhancement of blood fluidity. However, the exact mechanisms of how supercritical extracts of phalsak peel (SEPS) inhibits tumor metastasis and invasion are still not fully understood. We found that SEPS could downregulate the constitutive expression of both CXCR4 and HER2 in human breast cancer MDA‐MB‐231 cells as compared with other cells. SEPS also suppressed matrix metalloproteinase‐9 (MMP‐9) expression and its enzymatic activity under non‐cytotoxic concentrations. Neither proteasome inhibition nor lysosomal stabilization had any effect on the SEPS‐induced decrease in CXCR4 expression. A detailed study of the underlying molecular mechanisms revealed that the regulation of the downregulation of CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA expression, suppression of NF‐κB activity, and inhibition of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by SEPS correlated with the inhibition of CXCL12‐stimulated invasion of MDA‐MB‐231 cells. Overall, our results indicate, for the first time, that SEPS can suppress CXCR4 and MMP‐9 expressions through blockade of NF‐κB activation and thus has the potential to suppress metastasis of breast cancer. Copyright © 2014 John Wiley & Sons, Ltd.</div></front></TEI><affiliations><list><country><li>Corée du Sud</li></country><region><li>Région capitale de Séoul</li></region><settlement><li>Séoul</li></settlement></list><tree><country name="Corée du Sud"><region name="Région capitale de Séoul"><name sortKey="Kim, Chulwon" sort="Kim, Chulwon" uniqKey="Kim C" first="Chulwon" last="Kim">Chulwon Kim</name></region><name sortKey="Ahn, Kwang Seok" sort="Ahn, Kwang Seok" uniqKey="Ahn K" first="Kwang Seok" last="Ahn">Kwang Seok Ahn</name><name sortKey="Ahn, Kwang Seok" sort="Ahn, Kwang Seok" uniqKey="Ahn K" first="Kwang Seok" last="Ahn">Kwang Seok Ahn</name><name sortKey="Ahn, Kyoo Seok" sort="Ahn, Kyoo Seok" uniqKey="Ahn K" first="Kyoo Seok" last="Ahn">Kyoo Seok Ahn</name><name sortKey="Cho, Somi K" sort="Cho, Somi K" uniqKey="Cho S" first="Somi K." last="Cho">Somi K. Cho</name><name sortKey="Cho, Somi K" sort="Cho, Somi K" uniqKey="Cho S" first="Somi K." last="Cho">Somi K. Cho</name><name sortKey="Choi, Seung Oon" sort="Choi, Seung Oon" uniqKey="Choi S" first="Seung-Hoon" last="Choi">Seung-Hoon Choi</name><name sortKey="Chung, Won Eok" sort="Chung, Won Eok" uniqKey="Chung W" first="Won-Seok" last="Chung">Won-Seok Chung</name><name sortKey="Kim, Dongmin" sort="Kim, Dongmin" uniqKey="Kim D" first="Dongmin" last="Kim">Dongmin Kim</name><name sortKey="Kim, Sung Oon" sort="Kim, Sung Oon" uniqKey="Kim S" first="Sung-Hoon" last="Kim">Sung-Hoon Kim</name><name sortKey="Nam, Dongwoo" sort="Nam, Dongwoo" uniqKey="Nam D" first="Dongwoo" last="Nam">Dongwoo Nam</name><name sortKey="Shim, Bum Sang" sort="Shim, Bum Sang" uniqKey="Shim B" first="Bum Sang" last="Shim">Bum Sang Shim</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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