Nutrition Research and Practice

The Korean Nutrition Society (한국영양학회)
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Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells

  • Kim, Hyuck (Department of Diagnostics, College of Korean Medicine, Dongguk University) ;
  • Roh, Hyo Sun (Department of Acupoint, College of Korean Medicine, Dongguk University) ;
  • Kim, Jai Eun (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Park, Sun Dong (Department of Prescription, College of Korean Medicine, Dongguk University) ;
  • Park, Won Hwan (Department of Diagnostics, College of Korean Medicine, Dongguk University) ;
  • Moon, Jin-Young (Department of Acupoint, College of Korean Medicine, Dongguk University)
  • Received : 2015.08.13
  • Accepted : 2015.12.08
  • Published : 2016.06.01
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Abstract

BACKGROUND/OBJECTIVES: Stromal cell-derived growth factor 1 (SDF-1), also known as chemokine ligand 12, and chemokine receptor type 4 are involved in cancer cell migration. Compound K (CK), a metabolite of protopanaxadiol-type ginsenoside by gut microbiota, is reported to have therapeutic potential in cancer therapy. However, the inhibitory effect of CK on SDF-1 pathway-induced migration of glioma has not yet been established. MATERIALS/METHODS: Cytotoxicity of CK in C6 glioma cells was determined using an EZ-Cytox cell viability assay kit. Cell migration was tested using the wound healing and Boyden chamber assay. Phosphorylation levels of protein kinase C $(PKC){\alpha}$ and extracellular signal-regulated kinase (ERK) were measured by western blot assay, and matrix metallopeptidases (MMP) were measured by gelatin-zymography analysis. RESULTS: CK significantly reduced the phosphorylation of $PKC{\alpha}$ and ERK1/2, expression of MMP9 and MMP2, and inhibited the migration of C6 glioma cells under SDF-1-stimulated conditions. CONCLUSIONS: CK is a cell migration inhibitor that inhibits C6 glioma cell migration by regulating its downstream signaling molecules including $PKC{\alpha}$, ERK1/2, and MMPs.

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References

  1. Amberger VR, Hensel T, Ogata N, Schwab ME. Spreading and migration of human glioma and rat C6 cells on central nervous system myelin in vitro is correlated with tumor malignancy and involves a metalloproteolytic activity. Cancer Res 1998;58:149-58.
  2. Chintala SK, Rao JK. Invasion of human glioma: role of extracellular matrix proteins. Front Biosci 1996;1:d324-39. https://doi.org/10.2741/A135
  3. Stock AM, Hahn SA, Troost G, Niggemann B, Zanker KS, Entschladen F. Induction of pancreatic cancer cell migration by an autocrine epidermal growth factor receptor activation. Exp Cell Res 2014;326:307-14. https://doi.org/10.1016/j.yexcr.2014.04.022
  4. Lippitz BE. Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol 2013;14:e218-28. https://doi.org/10.1016/S1470-2045(12)70582-X
  5. Bajetto A, Barbieri F, Dorcaratto A, Barbero S, Daga A, Porcile C, Ravetti JL, Zona G, Spaziante R, Corte G, Schettini G, Florio T. Expression of CXC chemokine receptors 1-5 and their ligands in human glioma tissues: role of CXCR4 and SDF1 in glioma cell proliferation and migration. Neurochem Int 2006;49:423-32. https://doi.org/10.1016/j.neuint.2006.03.003
  6. Di Cesare S, Marshall JC, Fernandes BF, Logan P, Antecka E, Filho VB, Burnier MN Jr. In vitro characterization and inhibition of the CXCR4/CXCL12 chemokine axis in human uveal melanoma cell lines. Cancer Cell Int 2007;7:17. https://doi.org/10.1186/1475-2867-7-17
  7. Heckmann D, Maier P, Laufs S, Wenz F, Zeller WJ, Fruehauf S, Allgayer H. CXCR4 expression and treatment with SDF-$1{\alpha}$ or Plerixafor modulate proliferation and chemosensitivity of colon cancer cells. Transl Oncol 2013;6:124-32. https://doi.org/10.1593/tlo.12268
  8. Luker KE, Lewin SA, Mihalko LA, Schmidt BT, Winkler JS, Coggins NL, Thomas DG, Luker GD. Scavenging of CXCL12 by CXCR7 promotes tumor growth and metastasis of CXCR4-positive breast cancer cells. Oncogene 2012;31:4750-8. https://doi.org/10.1038/onc.2011.633
  9. Ray P, Lewin SA, Mihalko LA, Schmidt BT, Luker KE, Luker GD. Noninvasive imaging reveals inhibition of ovarian cancer by targeting CXCL12-CXCR4. Neoplasia 2011;13:1152-61. https://doi.org/10.1593/neo.111076
  10. Raman D, Baugher PJ, Thu YM, Richmond A. Role of chemokines in tumor growth. Cancer Lett 2007;256:137-65. https://doi.org/10.1016/j.canlet.2007.05.013
  11. Iwasa S, Yanagawa T, Fan J, Katoh R. Expression of CXCR4 and its ligand SDF-1 in intestinal-type gastric cancer is associated with lymph node and liver metastasis. Anticancer Res 2009;29:4751-8.
  12. Lahn MM, Sundell KL, Paterson BM. The role of protein kinase C-alpha in malignancies of the nervous system and implications for the clinical development of the specific PKC-alpha inhibitor aprinocarsen (Review). Oncol Rep 2004;11:515-22.
  13. Koivunen J, Aaltonen V, Peltonen J. Protein kinase C (PKC) family in cancer progression. Cancer Lett 2006;235:1-10. https://doi.org/10.1016/j.canlet.2005.03.033
  14. Troppmair J, Bruder JT, Munoz H, Lloyd PA, Kyriakis J, Banerjee P, Avruch J, Rapp UR. Mitogen-activated protein kinase/extracellular signal-regulated protein kinase activation by oncogenes, serum, and 12-O-tetradecanoylphorbol-13-acetate requires Raf and is necessary for transformation. J Biol Chem 1994;269:7030-5.
  15. Lee DC, Lau AS. Effects of Panax ginseng on tumor necrosis factor-$\alpha$-mediated inflammation: a mini-review. Molecules 2011;16:2802-16. https://doi.org/10.3390/molecules16042802
  16. Paul S, Shin HS, Kang SC. Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated from Korean ginseng (Panax ginseng C.A. Meyer). Food Chem Toxicol 2012;50:1354-61. https://doi.org/10.1016/j.fct.2012.02.035
  17. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT, Choi M, Naeem A. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  18. Hofseth LJ, Wargovich MJ. Inflammation, cancer, and targets of ginseng. J Nutr 2007;137 Suppl:183S-185S. https://doi.org/10.1093/jn/137.1.183S
  19. Yuan CS, Wang CZ, Wicks SM, Qi LW. Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res 2010;34:160-7. https://doi.org/10.5142/jgr.2010.34.3.160
  20. Qi LW, Wang CZ, Du GJ, Zhang ZY, Calway T, Yuan CS. Metabolism of ginseng and its interactions with drugs. Curr Drug Metab 2011;12:818-22. https://doi.org/10.2174/138920011797470128
  21. Chen Y, Xu Y, Zhu Y, Li X. Anti-cancer effects of ginsenoside compound k on pediatric acute myeloid leukemia cells. Cancer Cell Int 2013;13:24. https://doi.org/10.1186/1475-2867-13-24
  22. Wang CZ, Kim KE, Du GJ, Qi LW, Wen XD, Li P, Bauer BA, Bissonnette MB, Musch MW, Chang EB, Yuan CS. Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma. Am J Chin Med 2011;39:1161-71. https://doi.org/10.1142/S0192415X11009470
  23. Song G, Guo S, Wang W, Hu C, Mao Y, Zhang B, Zhang H, Hu T. Intestinal metabolite compound K of ginseng saponin potently attenuates metastatic growth of hepatocellular carcinoma by augmenting apoptosis via a Bid-mediated mitochondrial pathway. J Agric Food Chem 2010;58:12753-60. https://doi.org/10.1021/jf103814f
  24. Chae S, Kang KA, Chang WY, Kim MJ, Lee SJ, Lee YS, Kim HS, Kim DH, Hyun JW. Effect of compound K, a metabolite of ginseng saponin, combined with gamma-ray radiation in human lung cancer cells in vitro and in vivo. J Agric Food Chem 2009;57:5777-82. https://doi.org/10.1021/jf900331g
  25. Lee KP, Choi NH, Kim JT, Park IS. The effect of yacon (Samallanthus sonchifolius) ethanol extract on cell proliferation and migration of C6 glioma cells stimulated with fetal bovine serum. Nutr Res Pract 2015;9:256-61. https://doi.org/10.4162/nrp.2015.9.3.256
  26. Kobayashi T, Hattori S, Shinkai H. Matrix metalloproteinases-2 and -9 are secreted from human fibroblasts. Acta Derm Venereol 2003;83:105-7. https://doi.org/10.1080/00015550310007436
  27. Chinot OL, Macdonald DR, Abrey LE, Zahlmann G, Kerloëguen Y, Cloughesy TF. Response assessment criteria for glioblastoma: practical adaptation and implementation in clinical trials of antiangiogenic therapy. Curr Neurol Neurosci Rep 2013;13:347. https://doi.org/10.1007/s11910-013-0347-2
  28. Hess KR, Broglio KR, Bondy ML. Adult glioma incidence trends in the United States, 1977-2000. Cancer 2004;101:2293-9. https://doi.org/10.1002/cncr.20621
  29. Paek IB, Moon Y, Kim J, Ji HY, Kim SA, Sohn DH, Kim JB, Lee HS. Pharmacokinetics of a ginseng saponin metabolite compound K in rats. Biopharm Drug Dispos 2006;27:39-45. https://doi.org/10.1002/bdd.481
  30. Valenzuela-Fernandez A, Planchenault T, Baleux F, Staropoli I, Le-Barillec K, Leduc D, Delaunay T, Lazarini F, Virelizier JL, Chignard M, Pidard D, Arenzana-Seisdedos F. Leukocyte elastase negatively regulates Stromal cell-derived factor-1 (SDF-1)/CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4. J Biol Chem 2002;277:15677-89. https://doi.org/10.1074/jbc.M111388200
  31. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006;107:1761-7. https://doi.org/10.1182/blood-2005-08-3182
  32. Hattermann K, Mentlein R. An infernal trio: the chemokine CXCL12 and its receptors CXCR4 and CXCR7 in tumor biology. Ann Anat 2013;195:103-10. https://doi.org/10.1016/j.aanat.2012.10.013
  33. Mukherjee D, Zhao J. The role of chemokine receptor CXCR4 in breast cancer metastasis. Am J Cancer Res 2013;3:46-57.
  34. Ehtesham M, Min E, Issar NM, Kasl RA, Khan IS, Thompson RC. The role of the CXCR4 cell surface chemokine receptor in glioma biology. J Neurooncol 2013;113:153-62. https://doi.org/10.1007/s11060-013-1108-4
  35. do Carmo A, Patricio I, Cruz MT, Carvalheiro H, Oliveira CR, Lopes MC. CXCL12/CXCR4 promotes motility and proliferation of glioma cells. Cancer Biol Ther 2010;9:56-65. https://doi.org/10.4161/cbt.9.1.10342
  36. Jung SH, Woo MS, Kim SY, Kim WK, Hyun JW, Kim EJ, Kim DH, Kim HS. Ginseng saponin metabolite suppresses phorbol ester-induced matrix metalloproteinase-9 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathways in human astroglioma cells. Int J Cancer 2006;118:490-7. https://doi.org/10.1002/ijc.21356
  37. Fang W, Li H, Kong L, Niu G, Gao Q, Zhou K, Zheng J, Wu B. Role of matrix metalloproteinases (MMPs) in tumor invasion and metastasis: serial studies on MMPs and TIMPs. Beijing Da Xue Xue Bao 2003;35:441-3.

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