Browse > Article
http://dx.doi.org/10.5352/JLS.2019.29.5.514

Gene Expression Profiling by Ginsenoside Rb1 in Keratinocyte HaCaT Cells  

Lee, Dong Woo (Department of Biological Science and the Research Institute for Basic Sciences, Hoseo University)
Kim, Jung Min (Genoplan, Inc. & NAR Center, Inc.)
Bang, In Seok (Department of Biological Science and the Research Institute for Basic Sciences, Hoseo University)
Publication Information
Journal of Life Science / v.29, no.5, 2019 , pp. 514-523 More about this Journal
Abstract
We investigated the gene expression patterns and the mechanisms of action of the apoptotic response by microarray analysis of human keratinocyte HaCaT cells treated with ginsenoside Rb1, a saponin of Panax ginseng C. A. Meyer. Genes related to apoptosis, the G2/M transition of the mitotic cell cycle, cell division, mitotic nuclear division, and intracellular protein transport were 2-fold up-regulated in HaCaT cells treated with the ginsenoside Rb1, whereas genes related to DNA repair, regeneration fission, and extracellular matrix organization were 2-fold down-regulated. Apoptosis signaling may be mediated by FAS and PLA2G4A, and pathway analysis indicated that STAT3 might be an upstream regulator of these genes. The activity of FAS and PLA2G4A was verified by qPCR, which showed that FAS was increased about 2-fold in HaCaT cells treated with $10{\mu}g/ml$ of ginsenoside Rb1 for 24 hr, PLA2G4A was increased about twice after 6 hours, and gene expression was increased more than 2-fold after 24 hr. Knockdown of STAT3 with siRNA decreased FAS expression and increased PLA2G4A expression but only FAS was passed from the upstream regulator STAT3. These results indicate that STAT3, which is an upstream regulator, induces apoptosis via FAS during treatment with ginsenoside Rb1.
Keywords
Apoptosis; DNA microarray; FAS; Ginsenoside Rb1; HaCaT cells;
Citations & Related Records
Times Cited By KSCI : 7  (Citation Analysis)
연도 인용수 순위
1 Deng, G., Su, J. H., Ivins, K. J., Van Houten, B. and Cotman, C. W. 1999. Bcl-2 facilitates recovery from DNA damage after oxidative stress. Exp. Neurol. 159, 309-318.   DOI
2 Fung, C. K., Xi, N., Yang, R., Seiffert-Sinha, K. K., Lai, W. and Sinha, A. A. 2011. Quantitative analysis of human keratinocyte cell elasticity using atomic force microscopy (AFM). IEEE Trans. Nanobioscience 10, 9-15.   DOI
3 Halliwell, B., Gutteridge, J. M. C. and Cross, C. E. 1992. Free radicals, antioxidants, and human disease: Where are we now? J. Lab. Clin. Med. 119, 598-620.
4 Hasegawa, H. 2004. Proof of the mysterious efficacy of ginseng:basic and clinical trials: metabolic activation of ginsenoside:deglycosylation by intestinal bacteria and esterification with fatty acid. J. Pharmacol. Sci. 95, 153-157.   DOI
5 Hengartner, M. O. 2000. The biochemistry of apoptosis. Nature 407, 770-776.   DOI
6 Im, J. Y., Kim, B. K., Lee, J. Y., Park, S. H., Ban, H.S., Jung, K. E. and Won, M. 2018. DDIAS suppresses TRAIL-mediated apoptosis by inhibiting DISC formation and destabilizing caspase-8 in cancer cells. Oncogene 37, 1251-1262.   DOI
7 Inghirami, G., Chiarle, R., Simmons, W. J., Piva, R., Schlessinger, K. and Levy, D. E. 2005. New and old functions of STAT3: a pivotal target for individualized treatment of cancer. Cell Cycle 4, 1131-1133.   DOI
8 Kim, B. G., Choi, S. Y., Kim, M. R., Suh, H. J. and Park, H. J. 2010. Changes of ginsenosides in korean red ginseng (Panax ginseng) fermented by Lactobacillus plantarum M1. Process Biochem. 45, 1319-1324.   DOI
9 Kim, G., Sumiyoshi, M., Sakanaka, M. and Kimura, Y. 2009. Effects of ginseng saponins isolated from red ginseng on ultraviolet B-induced skin aging in hairless mice. Eur. J. Pharmacol. 602, 148-156.   DOI
10 Kim, H., Suh, J. M., Hwang, E. S., Kim, D. W., Chung, H. K., Song, J. H., Hwang, J. H., Park, K. C., Ro, H. K., Jo, E. K., Chang, J. S., Lee, T. H., Lee, M. S., Kohn, L. D. and Shong, M. 2003. Thyrotropin-mediated repression of class II trans-activator expression in thyroid cells: involvement of STAT3 and suppressor of cytokine signaling. J. Immunol. 171, 616-627.   DOI
11 Kimura, Y., Sumiyoshi, M. and Sakanaka, M. 2012. Effects of ginsenoside Rb1 on skin changes. J. Biomed. Biotechnol. 2012, 1-11.
12 Lee, J. O., Choi, E., Shin, K. K., Hong, Y. H., Kim, H. G., Jeong, D., Hossain, M. A., Kim, H. S., Yi, Y. S., Kim, D., Kim, E. and Cho, J. Y. 2019. Compound K, a ginsenoside metabolite, plays an antiinflammatory role in macrophages by targeting the AKT1-mediated signaling pathway. J. Ginseng Res. 43, 154-160.   DOI
13 Kramer, A., Green, J., Pollard, J. Jr. and Tugendreich, S. 2014. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30, 523-530.   DOI
14 Krammer, P. H., Arnold, R. and Lavrik, I. N. 2007. Life and death in peripheral T cells. Nat. Rev. Immunol. 7, 532-542.   DOI
15 Lee, C. H. and Kim, J. H. 2014. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J. Ginseng Res. 38, 161-166.   DOI
16 Lee, Y. M., Yoon, H., Park, H. M., Song, B. C. and Yeum, K. J. 2017. Implications of red Panax ginseng in oxidative stress associated chronic diseases. J. Ginseng Res. 41, 11311-119.
17 Lu, J. M., Yao, Q. and Chen, C. 2009. Ginseng compounds:an update on their molecular mechanisms and medical applications. Curr. Vasc. Pharmacol. 7, 293-302.   DOI
18 Mitchell, T. J. and John, S. 2005. Signal transducer and activator of transcription (STAT) signalling and T-cell lymphomas. Immunology 114, 301-312.   DOI
19 Park, J. H., Lee, Y. H., Kang, K. S., Lee, S. K., Kim, S. Z., Park, J. Y., Kwak, E. K. and Sohn, Y. K. 2004. The effects of ginsenoside Rb1 on the apoptosis and the production of nitric oxide in Rat C6 glioma cells. Kor. J. Pathol. 38, 1-7.
20 Namgoong, S., Lee, H., Han, S. K., Lee, H. W., Jeong, S. H. and Dhong, E. S. 2019. Effect of Panax ginseng extract on the activity of diabetic fibroblasts in vitro. Int. Wound J. 16, 737-745.   DOI
21 Park, S.E., Na, C. S., Yoo, S. A., Seo, S. H. and Son, H. S. 2017. Biotransformation of major ginsenosides in ginsenoside model culture by lactic acid bacteria. J. Ginseng Res. 41, 36-42.   DOI
22 Park, Y. J., Park, E. S., Kim, M. S., Kim, T. Y., Lee, H. S., Lee, S., Jang, I. S., Shong, M., Park, D. J. and Cho, B. Y. 2002. Involvement of the protein kinase C pathway in thyrotropin-induced STAT3 activation in FRTL-5 thyroid cells. Mol. Cell Endocrinol. 194, 77-84.   DOI
23 Richter, C., Gogvadze, V., Laffranchi, R., Schlapbach, R., Schweizer, M., Suter, M., Walter, P. and Yaffee, M. 1995. Oxidants in mitochondria: from physiology to diseases. Biochim. Biophys. Acta. 1271, 67-74.   DOI
24 Shibata, S. 2001. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J. Kor. Med. Sci. 16, 28-37.   DOI
25 Shin, J. E., Park, E. K., Kim, E. J., Hong, Y. H., Lee, K. T. and Kim, D. H. 2003. Cytotoxicity of compound K (IH-901) and ginsenoside Rh2, main biotransformants of ginseng saponins by bifidobacteria, against some tumor cells. J. Ginseng Res. 27, 129-134.   DOI
26 Simmler, C., Antheaume, C. and Lobstein, A. 2010. Antioxidant biomarkers from vanda coerulea stems reduce irradiated HaCaT PGE-2 production as a result of COX-2 inhibition. PLoS One 5, 1-9.
27 Zhang, G., Xia, F., Zhang, Y., Zhang, X., Cao, Y., Wang, L., Liu, X., Zhao, G. and Shi, M. 2016. Ginsenoside Rd is efficacious against acute ischemic stroke by suppressing microglial proteasome-mediated inflammation. Mol. Neurobiol. 53, 2529-2540.   DOI
28 Wakabayashi, C., Murakami, K., Hasegawa, H., Murata, J. and Saiki, I. 1998. An intestinal bacterial merabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem. Biophys. Res. Commun. 246, 725-730.   DOI
29 Yayeh, T, Jung, K. H., Jeong, H. Y., Park, J. H., Song, Y. B., Kwak, Y. S., Kang, H. S., Cho, J. Y., Oh, J. W. and Kim, S. K., et al. 2012. Korean red ginseng saponin fraction down regulates proinflammatory mediators in LPS stimulated RAW264.7 cells and protects mice against endotoxic shock. J. Ginseng Res. 36, 263-269.   DOI
30 Yoon, J. J., Jeong, J. W., Choi, E. O., Kim, M. J., Hwang-Bo, H., Kim, H. J., Hong, S. H., Park, C., Lee, D. H. and Choi, Y. H. 2017. Protective effects of Scutellaria baicalensis Georgi against hydrogen peroxide-induced DNA damage and apoptosis in HaCaT human skin keratinocytes. EXCLI J. 16, 426-438.   DOI
31 Degterev, A., Boyce, M. and Yuan, J. 2003. A decade of caspases. Oncogene 22, 8543-8567.   DOI
32 Attele, A. S., Wu, J. A. and Yuan, C. S. 1999. Ginseng pharmacology:multiple constituents and multiple actions. Biochem. Pharmacol. 58, 1685-1693.   DOI
33 Chim, C. S., Fung, T. K., Cheung, W. C., Liang, R. and Kwong, Y. L. 2004. SOCS1 and SHP1 hypermethylation in multiple myeloma: implications for epigenetic activation of the JAK/STAT pathway. Blood 103, 4630-4635.   DOI
34 Cho, W. J., Yoon, H. S., Kim, Y. H., Kim, J. M., Yoo, I. J., Han, M. D. and Bang, I. S. 2013. Cytoprotective effects and gene expression patterns observed based on the antioxidant activity of Lonicera japonica extract. J. Life Sci. 23, 989-997.   DOI
35 Choi, E. O., Kwon, D. H., Hwang, H. J., Kim, K. J., Lee, D. H. and Choi, Y. H. 2018. Antioxidant and cytoprotective effects of socheongja and socheong 2, Korean black seed coat soybean varieties, against hydrogen peroxide-induced oxidative damage in HaCaT human skin keratinocytes. J. Life Sci. 28, 454-464.   DOI
36 Choo, M. K., Sakurai. H., Kim. D. H. and Saiki, I. 2008. A ginseng saponin metabolite suppresses tumor necrosis factor-alpha-promoted metastasis by suppressing nuclear factor-kappaB signaling in murine colon cancer cells. Oncol. Rep. 19, 595-600.