Browse > Article
http://dx.doi.org/10.5352/JLS.2012.22.4.492

Curcumin Inhibits Cell Proliferation of Human Colorectal HCT116 Cells through Up-Regulation of Activating Transcription Factor 3 (ATF3)  

Kim, Hyo-Rim (Department of Biological Sciences, Andong National University)
Son, Jung-Bin (Department of Biological Sciences, Andong National University)
Lim, Seung-Hyun (Department of Biological Sciences, Andong National University)
Kim, Jong-Sik (Department of Biological Sciences, Andong National University)
Publication Information
Journal of Life Science / v.22, no.4, 2012 , pp. 492-498 More about this Journal
Abstract
To investigate whether phytochemicals affect cancer cell viability, human colorectal HCT116 cells were treated with four different phytochemicals. Among these phytochemicals, curcumin is the strongest inhibitor of cell proliferation. In addition, it decreased cell viability in a dose-dependent manner. To unveil the molecular mechanisms involved in the inhibition of cell proliferation by curcumin, we carried out oligo DNA microarray analysis. We found that 137 genes were up-regulated more than 2-fold, and 141 genes were down-regulated more than 2-fold by 25 ${\mu}M$ curcumin treatment. Among the up-regulated genes, we selected 3 genes (ATF-3, GADD45A, and NR4A1) to confirm microarray data. The results of RT-PCR strongly agreed with those of the microarray data. Among the phytochemicals used in this study, curcumin is the strongest inducer of ATF3 expression, and increased ATF3 expression in a dose-dependent manner. Interestingly, FACS analysis showed that the inhibition of cell growth by curcumin was recovered by ATF3-siRNA transfection. Finally, we detected the changes of gene expression by ectopic expression of ATF3. The results indicated that many up-regulated genes were related to apoptosis. Overall, these results suggest that ATF3 may play an important role in the anti-proliferative activity of curcumin in human colorectal cancer cells.
Keywords
Curcumin; cell proliferation; gene expression; ATF3; human colorectal cell;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Saha, A., T. Kuzuhara, N. Echigo, A. Fujii, M. Suganuma, and H. Fujiki. 2010. Apoptosis of human lung cancer cells by curcumin mediated through up-regulation of "growth arrest and DNA damage inducible genes 45 and 153. Biol. Pharm. Bull. 33, 1291-1299.   DOI   ScienceOn
2 Surh, Y. J. 2003. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer 3, 768-780.   DOI   ScienceOn
3 Whitlock, N. C., J. H. Bahn, S. H. Lee, T. E. Eling, and S. J. Baek. 2011. Resveratrol-induced apoptosis is mediated by early growth response-1, Kruppel-like factor 4, and activating transcription factor 3. Cancer Prev. Res. 4, 116-127.   DOI   ScienceOn
4 Wilken, R., M. S. Veena, M. B. Wang, and E. S. Srivatsan. 2011. Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol. Cancer 10, 1-19.   DOI   ScienceOn
5 Yan, C., M. S. Jamaluddin, B. Aggarwal, J. Myers, and D. D. Boyd. 2005. Gene expression profiling identifies activating transcription factor 3 as a novel contributor to the proapoptotic effect of curcumin. Mol. Cancer Ther. 4, 233-241.   DOI
6 Yoshida, A., Y. Pommier, and T. Ueda. 2006. Endonuclease activation and chromosomal DNA fragmentation during apoptosis in leukemia cells. Int. J. Hematol. 84, 31-37.   DOI
7 Yu, H., S. M. Kumar, D. Fang, G. Acs, and X. Xu. 2007. Nuclear orphan receptor TR3/Nur77 mediates melanoma cell apoptosis. Cancer Biol. Ther. 6, 405-412.   DOI   ScienceOn
8 Kaur, S., N. H. Modi, D. Panda, and N. Roy. 2010. Probing the binding site of curcumin in Escherichia coli and Bacillus subtilis FtsZ--a structural insight to unveil antibacterial activity of curcumin. Eur. J. Med. Chem. 45, 4209-4214.   DOI   ScienceOn
9 Khor, T. O., Y. Huang, T. Y. Wu, L. Shu, J. Lee, and A. N. Kong. 2011. Pharmacodynamics of curcumin as DNA hypomethylation agent in restoring the expression of Nrf2 via promoter CpGs demethylation. Biochem. Pharmacol. 82, 1073-1078.   DOI   ScienceOn
10 Kim, H. E., M. J. Jang, S. H. Lim, H. R. Kim, S. Y. Kim, G. J. Lee, and J. S. Kim. 2010. Analysis of p53 dependency of differentially expressed genes by capsaicin in human colorectal cancer cell. J. Life Sci. 20, 213-218.   DOI
11 Kolodziejczyk, J., B. Olas, J. Saluk-Juszczak, and B. Wachowicz. 2011. Antioxidative properties of curcumin in the protection of blood platelets against oxidative stress in vitro. Platelets 22, 270-276.   DOI   ScienceOn
12 Liao, S., J. Xia, Z. Chen, S. Zhang, A. Ahmad, L. Miele, F. H. Sarkar, and Z. Wang. 2011. Inhibitory effect of curcumin on oral carcinoma CAL-27 cells via suppression of Notch-1 and NF-$\kappa$B signaling pathways. J. Cell Biochem. 112, 1055-1065.   DOI   ScienceOn
13 Mudduluru, G., J. N. George-William, S. Muppala, I. A. Asangani, R. Kumarswamy, L. D. Nelson, and H. Allgayer. 2011. Curcumin regulates miR-21 expression and inhibits invasion and metastasis in colorectal cancer. Biosci. Rep. 31, 185-197.   DOI   ScienceOn
14 Park, C. E., H. Yun, E. B. Lee, B. I. Min, H. Bae, W. Choe, I. Kang, S. S. Kim, and J. Ha. 2010. The antioxidant effects of genistein are associated with AMP-activated protein kinase activation and PTEN induction in prostate cancer cells. J. Med. Food 13, 815-820.   DOI
15 Rajamanickam, S. and R. Agarwal. 2008. Natural products and colon cancer: current status and future prospects. Drug Dev. Res. 69, 460-471.   DOI   ScienceOn
16 Hartman, M. G., D. Lu, M. L. Kim, G. J. Kociba, T. Shukri, J. Buteau, X. Wang, W. L. Frankel, D. Guttridge, M. Prentki, S. T. Grey, D. Ron, and T. Hai. 2004. Role for activating transcription factor 3 in stress-induced beta-cell apoptosis. Mol. Cell Biol. 24, 5721-5732.   DOI   ScienceOn
17 Reuter, S., S. C. Gupta, B. Park, A. Goel, and B. B. Aggarwal. Epigenetic changes induced by curcumin and other natural compounds. Genes Nutr. 6, 93-108.
18 Chang, L. F., P. C. Lin, L. I. Ho, P. Y. Liu, W. C. Wu, I. P. Chiang, H. W. Chang, S. Z. Lin, Y. C. Harn, H. J. Harn, and T. W. Chiou. 2011. Overexpression of the orphan receptor Nur77 and its translocation induced by PCH4 may inhibit malignant glioma cell growth and induce cell apoptosis. J. Surg. Oncol. 103, 442-450.   DOI   ScienceOn
19 Das, S. and D. K. Das. 2007. Anti-inflammatory responses of resveratrol. Inflamm. Allergy Drug Targets 6, 168-173.   DOI   ScienceOn
20 Jacob, A., R. Wu, M. Zhou, and P. Wang. 2007. Mechanism of the anti-inflammatory effect of curcumin: PPAR-gamma. PPAR Res. 2007, 1-5.
21 Jang, M. J., H. E. Kim, S. M. Son, M. J. Kim, E. W. Seo, Y. H. Kim, and J. S. Kim. 2009. Over-expression of NSAID activated gene-1 by caffeic acid phenethyl ester. J. Life Sci. 19, 1787-1793.   DOI