Browse > Article
http://dx.doi.org/10.5352/JLS.2012.22.1.55

Anti-Proliferative Effects of Selenium in HT-29 Colon Cancer Cells via Inhibition of Akt  

Park, Song-Yi (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Kim, In-Seop (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Lee, Se-Hee (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Lee, Sol-Hwa (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Jung, Da-Woon (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Park, Ock-Jin (Department of Food and Nutrition, College of Life Science and Nano Technology, Hannam University)
Kim, Young-Min (Department of Biological Sciences, College of Life Science and Nano Technology, Hannam University)
Publication Information
Journal of Life Science / v.22, no.1, 2012 , pp. 55-61 More about this Journal
Abstract
Akt is known to play an important role in cell proliferation and differentiation, and is also over-expressed in several types of cancer cells. In this study, we explored the anti-proliferative effects of selenium in HT-29 colon cancer cells, mediated through effects on Akt and COX-2. Selenium treatments at different concentrations and for different durations inhibited proliferation of HT-29 colon cancer cells and increased apoptotic cell death. Selenium treatment decreased Akt phosphorylation and COX-2 expression. Treatment with LY294002 (an Akt inhibitor) decreased proliferation of HT-29 cells, while a combined treatment with LY294002 and selenium resulted in even further decreases in cell proliferation. Inactivation of Akt by Akt siRNA treatment abolished these inhibitory effects on cell growth. COX-2 expression decreased in Akt transfected cells compared to non-transfected cells. These results suggest that selenium induced both anti-proliferative and apoptotic effects by inhibiting Akt phosphorylation and COX-2 expression. Selenium treatment also appeared to induce synergistic anti-proliferative effects by inhibition of Akt in HT-29 colon cancer cells.
Keywords
Selenium; anti-proliferatory effect; HT-29 colon cancer cells; Akt siRNA; COX-2;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Lee, Y. K., S. Y. Park, Y. M. Kim, D. C. Kim, W. S. Lee, Y. J. Surh, and O. J. Park. 2010. Suppression of mTOR via Akt-dependent and -independent mechanisms in selenium- treated colon cancer cells: involvement of AMPKalpha1. Carcinogenesis 31, 1092-1099.   DOI   ScienceOn
2 Li, X. Y., X. R. Zhan, X. M. Liu, and X. C. Wang. 2011. CREB is a regulatory target for the protein kinase Akt/PKB in the differentiation of pancreatic ductal cells into islet $\beta$-cells mediated by hepatocyte growth factor. Biochem. Biophys. Res. Commun. 404, 711-716.   DOI   ScienceOn
3 Li, Y. B., J. Y. Han, W. Jiang, and J. Wang. 2011. Selenium inhibits high glucose-induced cyclooxygenase-2 and P-selectin expression in vascular endothelial cells. Mol. Biol. Rep. 38, 2301-2306.   DOI   ScienceOn
4 Osaki, M., M. Oshimura, and H. Ito 2004. PI3K/Akt pathway: its functions and alterations in human cancer. Apoptosis 9, 667-676.   DOI
5 Rotruck, J. T., A. L. Pope, H. E. Ganther, A. B. Swanson, D. G. Hafeman, and W. G. 1973. Hoekstra. Selenium: biochemical role as a component of glutathione peroxidase. Science 179, 588-90.   DOI   ScienceOn
6 Rotruck, J. T., W. G. Hoekstra, H. E. Ganther, and A. L. Pope. 1972. Prevention of oxidative damage to rat erythrocytes by dietary selenium. J. Nutr. 120, 689.
7 Rudolf, E., V. Kralova, and M. Cervinka. 2008. Selenium and colon cancer--from chemoprevention to new treatment modality. Anticancer Agents Med. Chem. 8. 598-602.   DOI
8 Bellacosa, A., C. C. Kumar, C. A. Di, and J. R. Testa. 2005. Activation of Akt kinases in cancer implications for therapeutic targeting. Adv. Cancer Res. 94, 29-86.   DOI
9 Carnero, A. 2010. The PKB/AKT pathway in cancer. Curr. Pharm. Des. 16, 34-44.   DOI   ScienceOn
10 Chao, X., J. Zao, G. Xiao-Yi, M. Li-Jun, and S. Tao. 2010. Blocking of PI3K/AKT induces apoptosis by its effect on $NF-{\kappa}B$ activity in gastric carcinoma cell line SGC7901. Biomed. Pharmacother. 64. 600-604.   DOI   ScienceOn
11 Clark, L. C., G. F. Jr. Combs, B. W. Turnbull, E. H. Slate, D. K. Chalker, J. Chow, L. S. Davis, R. A. Glover, G. F. Graham, E. G. Gross, A. Krongrad, J. L. Jr. Lesher, H. K. Park, B. B. Jr. Sanders, C. L. Smith, and J. R. Taylor. 1996. Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional prevention of cancer trial. JAMA 276, 1957-1963.   DOI   ScienceOn
12 Glynn, S. A., R. L. Prueitt, L. A. Ridnour, B. J. Boersma, T. M. Dorsey, D. A. Wink, J. E. Goodman, H. G. Yfantis, D. H. Lee, and S. Ambs. 2010. COX-2 activation is associated with Akt phosphorylation and poor survival in ER-negative, HER2-positive breast cancer. BMC Cancer 10, 626.   DOI
13 Sinha, R., S. C. Kiley, J. X. Lu, H. J. Thompson, R. Moraes, S. Jaken, and D. Medina. 1999. Effects of methylselenocysteine on PKC activity, cdk2 phosphorylation and gadd gene expression in synchronized mouse mammary epithelial tumor cells. Cancer Lett. 146, 135-145.   DOI   ScienceOn
14 Tang, C. H., R. S. Yang, T. H. Huang, D. Y. Lu, W. J. Chuang, T. F. Huang, and W. M. Fu. 2006. Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts. Mol. Pharmacol. 69, 2047-2057.   DOI   ScienceOn
15 El-Bayoumy, K. 2001. The protective role of selenium on genetic damage and on cancer. Mutat. Res. 475, 123-139.   DOI
16 Gopalakrishna, R., Z. H. Chen, and U. Gundimeda. 1997. Seleno-compounds induce a redox modulation of protein kinase C in the cell, compartmentally independent from cytosolic glutathione: its role in inhibition of tumor promotion. Arch. Biochem. Biophys. 348, 37-48.   DOI   ScienceOn
17 Han, Y. D., Y. K. Hong, J. G. Kang, Y. J. Choi, and C. H. Park. 2010. Relation of the expression of cyclooxygenase-2 in colorectal adenomas and adenocarcinomas to angiogenesis and prognosis. J. Korean Soc. Coloproctol. 26, 339-346.   DOI
18 Kada, F., M. Saji, and M. D. Ringel. 2004. Akt: a potential target for thyroid cancer therapy. Curr. Drug Targets Immune Endocr. Metabol. Disord. 4, 181-185.   DOI   ScienceOn
19 Korkaya, H., A. Paulson, E. Charafe-Jauffret, C. Ginestier, M. Brown, J. Dutcher, S. G. Clouthier, and M. S. Wicha. 2009. Regulation of mammary stem/progenitor cells by PTEN/Akt/beta-catenin signaling. PLoS Biol. 7, e1000121.   DOI
20 Yamauchi, T., M. Watanabe, T. Kubota, H. Hasegawa, Y. Ishii, T. Endo, Y. Kabeshima, K. Yorozuya, K. Yamamoto M. Mukai, and M. Kitajima. 2002. Cyclooxygenase-2 expression as a new marker for patients with colorectal cancer. Dis. Colon Rectum. 45, 98-103.   DOI   ScienceOn
21 Lee, Y. K., S. Y. Park, Y. M. Kim, and O. J. Park. 2009. Regulatory effect of the AMPK-COX-2 signaling pathway in curcumin-induced apoptosis in HT-29 colon cancer cells. Ann. N. Y. Acad. Sci. 1171, 489-494.   DOI   ScienceOn
22 Lee, K. M., M. K. Hwang, D. E. Lee, K. W. Lee, and H. J. Lee. 2010. Protective effect of quercetin against arsenite-induced COX-2 expression by targeting PI3K in rat liver epithelial cells. J. Agric. Food Chem. 58, 5815-5820.   DOI   ScienceOn
23 Lee, S. H., S. Y. Park, I. S. Kim, O. J. Park, and Y. M. Kim 2010. The effect of combind treatment of selenium and curcumin on Akt and mTOR regulation in Hep3B hepato- carcinoma cells. Cancer Prev. Res. 15. 285-290.