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Research ArticleArticle

Anti-Invasive Gene Expression Profile of Curcumin in Lung Adenocarcinoma Based on a High Throughput Microarray Analysis

Huei-Wen Chen, Sung-Liang Yu, Jeremy J. W. Chen, Han-Ni Li, Yi-Chen Lin, Pei-Li Yao, Han-Yi Chou, Chiang-Ting Chien, Wen-Jone Chen, Yuan-Teh Lee and Pan-Chyr Yang
Molecular Pharmacology January 2004, 65 (1) 99-110; DOI: https://doi.org/10.1124/mol.65.1.99
Huei-Wen Chen
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Sung-Liang Yu
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Jeremy J. W. Chen
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Han-Ni Li
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Yi-Chen Lin
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Pei-Li Yao
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Han-Yi Chou
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Chiang-Ting Chien
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Wen-Jone Chen
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Yuan-Teh Lee
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Pan-Chyr Yang
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Abstract

Curcumin has been reported to exhibit anti-invasive and/or antimetastatic activities, but the mechanism remains unclear. In this study, microarray analysis of gene expression profiles were used to characterize the anti-invasive mechanisms of curcumin in highly invasive lung adenocarcinoma cells (CL1-5). Results showed that curcumin significantly reduces the invasive capacity of CL1-5 cells in a concentration range far below its levels of cytotoxicity (20 μM) and that this anti-invasive effect was concentration dependent (10.17 ± 0.76 × 103 cells at 0 μM; 5.67 ± 1.53 × 103 cells at 1 μM; 2.67 ± 0.58 × 103 cells at 5 μM; 1.15 ± 1.03 × 103 cells at 10 μM; P < 0.05) in the Transwell cell culture chamber assay. Using microarray analysis, 81 genes were down-regulated and 71 genes were up-regulated after curcumin treatment. Below sublethal concentrations of curcumin (10 μM), several invasion-related genes were suppressed, including matrix metalloproteinase 14 (MMP14; 0.65-fold), neuronal cell adhesion molecule (0.54-fold), and integrins α6 (0.67-fold) and β4 (0.63-fold). In addition, several heat-shock proteins (Hsp) [Hsp27 (2.78-fold), Hsp70 (3.75-fold), and Hsp40-like protein (3.21-fold)] were induced by curcumin. Real-time quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry confirmed these results in both RNA and protein levels. Curcumin (1 to 10 μM) reduced the MMP14 expression in both mRNA and protein levels and also inhibited the activity of MMP2, the down-stream gelatinase of MMP14, by gelatin zymographic analysis. Based on these data, it can be concluded that curcumin might be an effective antimetastatic agent with a mechanism of anti-invasion via the regulation of certain gene expressions.

  • Received June 12, 2003.
  • Accepted October 10, 2003.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 65 (1)
Molecular Pharmacology
Vol. 65, Issue 1
1 Jan 2004
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Research ArticleArticle

Anti-Invasive Gene Expression Profile of Curcumin in Lung Adenocarcinoma Based on a High Throughput Microarray Analysis

Huei-Wen Chen, Sung-Liang Yu, Jeremy J. W. Chen, Han-Ni Li, Yi-Chen Lin, Pei-Li Yao, Han-Yi Chou, Chiang-Ting Chien, Wen-Jone Chen, Yuan-Teh Lee and Pan-Chyr Yang
Molecular Pharmacology January 1, 2004, 65 (1) 99-110; DOI: https://doi.org/10.1124/mol.65.1.99

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Research ArticleArticle

Anti-Invasive Gene Expression Profile of Curcumin in Lung Adenocarcinoma Based on a High Throughput Microarray Analysis

Huei-Wen Chen, Sung-Liang Yu, Jeremy J. W. Chen, Han-Ni Li, Yi-Chen Lin, Pei-Li Yao, Han-Yi Chou, Chiang-Ting Chien, Wen-Jone Chen, Yuan-Teh Lee and Pan-Chyr Yang
Molecular Pharmacology January 1, 2004, 65 (1) 99-110; DOI: https://doi.org/10.1124/mol.65.1.99
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