QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, H.-W. Articles by Yang, P.-C. Search for Related Content PubMed PubMed Citation Articles by Chen, H.-W. Articles by Yang, P.-C.

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

Departments of Medical Research (H.-W.C., J.J.W.C., C.T.C.), Surgery (S.-L.Y.), and Internal Medicine (Y.-C.L., P.-L.Y., W.-J.C., Y.-T.L., P.-C.Y.), National Taiwan University Hospital and Institute of Molecular Medicine (H.-Y.C.), National Taiwan University College of Medicine, Taipei, Taiwan; Taipei Medical University, Taipei, Taiwan (H.-W.C., H.-N.L.); Department of Life Science (H.-W.C.), Institute of Biomedical Sciences, and Molecular Biology (J.J.W.C.), College of Life Science, National Chung-Hsing University, Taichung, Taiwan, Republic of China

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 x 10³ cells at 0 µM; 5.67 ± 1.53 x 10³ cells at 1 µM; 2.67 ± 0.58 x 10³ cells at 5 µM; 1.15 ± 1.03 x 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 6 (0.67-fold) and 4 (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.

Address correspondence to: Dr. Pan-Chyr Yang, Department of Internal Medicine, National Taiwan University Hospital, 7 Chung Shan South Road, Taipei, Taiwan 100, ROC. E-mail: pcyang{at}ha.mc.ntu.edu.tw

This article has been cited by other articles:

				H.-W. Chen, J.-Y. Lee, J.-Y. Huang, C.-C. Wang, W.-J. Chen, S.-F. Su, C.-W. Huang, C.-C. Ho, J. J.W. Chen, M.-F. Tsai, et al. Curcumin Inhibits Lung Cancer Cell Invasion and Metastasis through the Tumor Suppressor HLJ1 Cancer Res., September 15, 2008; 68(18): 7428 - 7438. [Abstract] [Full Text] [PDF]

				K. K. Meja, S. Rajendrasozhan, D. Adenuga, S. K. Biswas, I. K. Sundar, G. Spooner, J. A. Marwick, P. Chakravarty, D. Fletcher, P. Whittaker, et al. Curcumin Restores Corticosteroid Function in Monocytes Exposed to Oxidants by Maintaining HDAC2 Am. J. Respir. Cell Mol. Biol., September 1, 2008; 39(3): 312 - 323. [Abstract] [Full Text] [PDF]

				M.-F. Tsai, C.-C. Wang, G.-C. Chang, C.-Y. Chen, H.-Y. Chen, C.-L. Cheng, Y.-P. Yang, C.-Y. Wu, F.-Y. Shih, C.-C. Liu, et al. A new tumor suppressor DnaJ-like heat shock protein, HLJ1, and survival of patients with non-small-cell lung carcinoma. J Natl Cancer Inst, June 21, 2006; 98(12): 825 - 838. [Abstract] [Full Text] [PDF]

				G. P. Collett and F. C. Campbell Overexpression of p65/RelA potentiates curcumin-induced apoptosis in HCT116 human colon cancer cells Carcinogenesis, June 1, 2006; 27(6): 1285 - 1291. [Abstract] [Full Text] [PDF]

				D. R. Yance Jr and S. M. Sagar Targeting angiogenesis with integrative cancer therapies. Integr Cancer Ther, March 1, 2006; 5(1): 9 - 29. [Abstract] [PDF]

				H.-W. Chen, J. J.W. Chen, S.-L. Yu, H.-N. Li, P.-C. Yang, C.-M. Su, H.-K. Au, C.-W. Chang, L.-W. Chien, C.-S. Chen, et al. Transcriptome analysis in blastocyst hatching by cDNA microarray Hum. Reprod., September 1, 2005; 20(9): 2492 - 2501. [Abstract] [Full Text] [PDF]