Browse > Article
http://dx.doi.org/10.1016/j.jgr.2016.07.006

Korean Red Ginseng water extract arrests growth of xenografted lymphoma cells  

Park, Jae Gwang (Department of Genetic Engineering, Sungkyunkwan University)
Son, Young-Jin (Department of Pharmacy, Sunchon National University)
Aravinthan, Adithan (Department of Physiology, College of Veterinary Medicine, Chonbuk National University)
Kim, Jong-Hoon (Department of Physiology, College of Veterinary Medicine, Chonbuk National University)
Cho, Jae Youl (Department of Genetic Engineering, Sungkyunkwan University)
Publication Information
Journal of Ginseng Research / v.40, no.4, 2016 , pp. 431-436 More about this Journal
Abstract
Background: Although numerous studies of the anticancer activities of Korean Red Ginseng (KRG) have been performed, the therapeutic effect of KRG on leukemia has not been fully elucidated. In this study, we investigated the antileukemia activities of KRG and its cellular and molecular mechanisms. Methods: An established leukemia tumor model induced by xenografted T cell lymphoma (RMA cells) was used to test the therapeutic activity of KRG water extract (KRG-WE). Direct cytotoxic activity of KRG-WE was confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The immunomodulatory activities of KRG-WE were verified by immunohistochemistry, nitric oxide production assay. The inhibitory effect of KRG-WE on cell survival signaling was also examined. Results: Orally administered KRG-WE reduced the sizes of tumor masses. Levels of apoptosis regulatory enzymes and cleaved forms of caspases-3 and -8 were increased by this extract. In addition, expression of matrix metalloproteinase-9, a metastasis regulatory enzyme, was decreased by KRG-WE treatment. The proportion of CD11c+ cells was remarkably increased in the KRG-treated group compared to the control group. However, KRG-WE did not show significant direct cytotoxicity against RMA cells. Conclusion: Our results strongly suggest that the KRG might have antileukemia activity through CD11c+ cell-mediated antitumor immunity.
Keywords
anticancer activity; cytotoxicity; Korean Red Ginseng; leukemia; Panax ginseng;
Citations & Related Records
Times Cited By KSCI : 10  (Citation Analysis)
연도 인용수 순위
1 Mao Q, Zhang PH, Wang Q, Li SL. Ginsenoside F 2 induces apoptosis in humor gastric carcinoma cells through reactive oxygen species-mitochondria pathway and modulation of ASK-1/JNK signaling cascade in vitro and in vivo. Phytomedicine 2014;21:515-22.   DOI
2 Park JG, Kang WS, Park KT, Park DJ, Aravinthan A, Kim JH, Cho JY. Anticancer effect of joboksansam, Korean wild ginseng germinated from bird feces. J Ginseng Res 2016;40:304-8.   DOI
3 Jung H, Bae J, Ko SK, Sohn UD. Ultrasonication processed Panax ginseng berry extract induces apoptosis through an intrinsic apoptosis pathway in HepG2 cells. Arch Pharm Res 2016;39:855-62.   DOI
4 Park TY, Park MH, Shin WC, Rhee MH, Seo DW, Cho JY, Kim HM. Anti-metastatic potential of ginsenoside Rp1, a novel ginsenoside derivative. Biol Pharm Bull 2008;31:1802-5.   DOI
5 Byeon SE, Lee J, Kim JH, Yang WS, Kwak YS, Kim SY, Choung ES, Rhee MH, Cho JY. Molecular mechanism of macrophage activation by red ginseng acidic polysaccharide from Korean Red Ginseng. Mediators Inflamm 2012;2012:732860.
6 Du XF, Jiang CZ, Wu CF, Won EK, Choung SY. Synergistic immunostimulating activity of pidotimod and red ginseng acidic polysaccharide against cyclophosphamide-induced immunosuppression. Arch Pharm Res 2008;31:1153-9.   DOI
7 Wang L, Yao Y, Sang W, Yang X, Ren G. Structural features and immunostimulating effects of three acidic polysaccharides isolated from Panax quinquefolius. Int J Biol Macromol 2015;80:77-86.   DOI
8 Choi KT. Botanical characteristics, pharmacological effects and medicinal components of Korean Panax ginseng C A Meyer. Acta Pharmacol Sin 2008;29:1109-18.   DOI
9 Kim SH, Cho SS, Simkhada JR, Lee HJ, Kim SW, Kim TS, Yoo JC. Enhancement of 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced HL-60 leukemia cell differentiation by Panax ginseng. Biosci Biotechnol Biochem 2009;73:1048-53.   DOI
10 Durairaj P, Miller SC. Neoplasm prevention and immuno-enhancement mediated by daily consumption of a proprietary extract from North American ginseng by elderly mice of a cancer-prone strain. Phytother Res 2013;27:1339-44.   DOI
11 Jo S, Lee H, Kim S, Lee CH, Chung H. Korean Red Ginseng extract induces proliferation to differentiation transition of human acute promyelocytic leukemia cells via MYC-SKP2-CDKN1B axis. J Ethnopharmacol 2013;150:700-7.   DOI
12 De Bruijn ML, Schumacher TN, Nieland JD, Ploegh HL, Kast WM, Melief CJ. Peptide loading of empty major histocompatibility complex molecules on RMA-S cells allows the induction of primary cytotoxic T lymphocyte responses. Eur J Immunol 1991;21:2963-70.   DOI
13 Park SE, Park C, Kim SH, Hossain MA, Kim MY, Chung HY, Son WS, Kim GY, Choi YH, Kim ND. Korean Red Ginseng extract induces apoptosis and decreases telomerase activity in human leukemia cells. J Ethnopharmacol 2009;121:304-12.   DOI
14 Endale M, Park SC, Kim S, Kim SH, Yang Y, Cho JY, Rhee MH. Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-${\kappa}B$-induced inflammatory mediators production in RAW 264.7 cells. Immunobiology 2013;218:1452-67.   DOI
15 Piao J, Lee JY, Weon JB, Ma CJ, Ko HJ, Kim DD, Kang WS, Cho HJ. Angelica gigas Nakai and Soluplus-based solid formulations prepared by hot-melting extrusion: Oral absorption enhancing and memory ameliorating effects. PLoS One 2015;10:e0124447.   DOI
16 Cho JY, Kim AR, Yoo ES, Baik KU, Park MH. Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation. Planta Med 2002;68:497-500.   DOI
17 Park JG, Kim SC, Kim YH, Yang WS, Kim Y, Hong S, Kim KH, Yoo BC, Kim SH, Kim JH, et al. Anti-inflammatory and antinociceptive activities of anthraquinone-2-carboxylic acid. Mediators Inflamm 2016;2016:1903849.
18 Vivanco I, Sawyers CL. The phosphatidylinositol 3-kinase-AKT pathway in human cancer. Nature Rev Cancer 2002;2:489-501.   DOI
19 Yayeh T, Jung KH, Jeong HY, Park JH, Song YB, Kwak YS, Kang HS, Cho JY, Oh JW, Kim SK. Korean Red Ginseng saponin fraction downregulates proinflammatory mediators in LPS stimulated RAW264. 7 cells and protects mice against endotoxic shock. J Ginseng Res 2012;36:263-9.   DOI
20 Devarajan E, Sahin AA, Chen JS, Krishnamurthy RR, Aggarwal N, Brun AM, Sapino A, Zhang F, Sharma D, Yang XH. Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene 2002;21:8843-51.   DOI
21 Merdad A, Karim S, Schulten HJ, Dallol A, Buhmeida A, Al-Thubaity F, Gari MA, Chaudhary AG, Abuzenadah AM, Al-Qahtani MH. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer: MMP-9 as a potential biomarker for cancer invasion and metastasis. Anticancer Res 2014;34:1355-66.
22 Wang CZ, Yuan CS. Potential role of ginseng in the treatment of colorectal cancer. Am J Chin Med 2008;36:1019-28.   DOI
23 Hume DA, Perry VH, Gordon S. Immunohistochemical localization of a macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglial cells to form a regular array in the plexiform layers. J Cell Biol 1983;97:253-7.   DOI
24 Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, Ott G, Muller-Hermelink HK, Campo E, Braziel RM, Jaffe ES. Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood 2004;103:275-82.   DOI
25 Lee JJ, Kwon HK, Jung IH, Cho YB, Kim KJ, Kim JL. Anticancer activities of ginseng extract fermented with Phellinus linteus. Mycobiology 2009;37:21-7.   DOI
26 Lv Q, Rong N, Liu LJ, Xu XL, Liu JT, Jin FX, Wang CM. Antitumoral activity of (20R)- and (20S)-ginsenoside Rh2 on transplanted hepatocellular carcinoma in mice. Planta Med 2016;82:705-11.   DOI
27 Seo EY, Kim WK. Red ginseng extract reduced metastasis of colon cancer cells in vitro and in vivo. J Ginseng Res 2011;35:315-24.   DOI
28 Kim SJ, Kim AK. Anti-breast cancer activity of fine black ginseng (Panax ginseng Meyer) and ginsenoside Rg5. J Ginseng Res 2015;39:125-34.   DOI
29 Xiaoguang C, Hongyan L, Xiaohong L, Zhaodi F, Yan L, Lihua T, Rui H. Cancer chemopreventive and therapeutic activities of red ginseng. J Ethnopharmacol 1998;60:71-8.   DOI
30 Kim JH, Hahm DH, Yang DC, Kim JH, Lee HJ, Shim I. Effect of crude saponin of Korean Red Ginseng on high-fat diet-induced obesity in the rat. J Pharmacol Sci 2005;97:124-31.   DOI
31 Nabavi SF, Sureda A, Habtemariam S, Nabavi SM. Ginsenoside Rd and ischemic stroke; a short review of literatures. J Ginseng Res 2015;39:299-303.   DOI
32 Kang S, Min H. Ginseng, the 'immunity boost': the effects of Panax ginseng on immune system. J Ginseng Res 2012;36:354-68.   DOI
33 Wang CZ, Cai Y, Anderson S, Yuan CS. Ginseng metabolites on cancer chemoprevention: an angiogenesis link? Diseases 2015;3:193-204.   DOI
34 Choi K, Choi C. Proapoptotic ginsenosides Compound K and Rh 2 enhance Fas-induced cell death of human astrocytoma cells through distinct apoptotic signaling pathways. Cancer Res Treat 2009;41:36-44.   DOI
35 Wong VK, Cheung SS, Li T, Jiang ZH, Wang JR, Dong H, Yi XQ, Zhou H, Liu L. Asian ginseng extract inhibits in vitro and in vivo growth of mouse lewis lung carcinoma via modulation of ERK-p53 and NF-kappaB signaling. J Cell Biochem 2010;111:899-910.   DOI
36 Wang CZ, Anderson S, Du W, He TC, Yuan CS. Red ginseng and cancer treatment. Chin J Nat Med 2016;14:7-16.
37 Park JM, Lee HJ, Yoo JH, Ko WJ, Cho JY, Hahm KB. Overview of gastrointestinal cancer prevention in Asia. Best Pract Res Clin Gastroenterol 2015;29:855-67.   DOI
38 Gao M, Kong Y, Yang G, Gao L, Shi J. Multiple myeloma cancer stem cells. Oncotarget 2016. http://dx.doi.org/10.18632/oncotarget.8154.   DOI
39 Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J. Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 2005;105:2214-9.   DOI
40 Kim HS, Lim JM, Kim JY, Kim Y, Park S, Sohn J. Panaxydol, a component of Panax ginseng, induces apoptosis in cancer cells through EGFR activation and ER stress and inhibits tumor growth in mouse models. Int J Cancer 2016;138:1432-41.   DOI
41 Kim MY, Yoo BC, Cho JY. Ginsenoside-Rp1-induced apolipoprotein A-1 expression in the LoVo human colon cancer cell line. J Ginseng Res 2014;38:251-5.   DOI
42 Wang JH, Nao JF, Zhang M, He P. 20 (s)-ginsenoside Rg3 promotes apoptosis in human ovarian cancer HO-8910 cells through PI3K/Akt and XIAP pathways. Tumor Biol 2014;35:11985-94.   DOI