Compound K attenuates stromal cell-derived growth factor 1 (SDF-1)-induced migration of C6 glioma cells
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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)α 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 PKCα 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 PKCα, ERK1/2, and MMPs.
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)α 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 PKCα 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 PKCα, ERK1/2, and MMPs.
참고문헌 (37)
- Amberger VR, "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, 58, pp.149~158 (1998)
- Chintala SK, "Invasion of human glioma: role of extracellular matrix proteins", Front Biosci, 1, pp.d324~d339 (1996)
- Stock AM, "Induction of pancreatic cancer cell migration by an autocrine epidermal growth factor receptor activation", Exp Cell Res, 326, pp.307~314 (2014)
- Lippitz BE., "Cytokine patterns in patients with cancer: a systematic review", Lancet Oncol, 14, pp.e218~e228 (2013)
- Bajetto A, "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, 49, pp.423~432 (2006)
- Di Cesare S, "In vitro characterization and inhibition of the CXCR4", CXCL12 chemokine axis in human uveal melanoma cell lines, 2007, pp.7, 17~
- Heckmann D, "CXCR4 expression and treatment with SDF-1α or Plerixafor modulate proliferation and chemosensitivity of colon cancer cells", Transl Oncol, 6, pp.124~132 (2013)
- Luker KE, "Scavenging of CXCL12 by CXCR7promotes tumor growth and metastasis of CXCR4-positive breast cancer cells", Oncogene, 31, pp.4750~4758 (2012)
- Ray P, "Noninvasive imaging reveals inhibition of ovarian cancer by targeting CXCL12-CXCR4", Neoplasia, 13, pp.1152~1161 (2011)
- Raman D, "Role of chemokines in tumor growth", Cancer Lett, 256, pp.137~165 (2007)
- Iwasa S, "Expression of CXCR4 and its ligand SDF-1 in intestinal-type gastric cancer is associated with lymph node and liver metastasis", Anticancer Res, 29, pp.4751~4758 (2009)
- Lahn MM, "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, 11, pp.515~522 (2004)
- Koivunen J, "Protein kinase C (PKC) family in cancer progression", Cancer Lett, 235, pp.1~10 (2006)
- Troppmair J, "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, 1994, pp.269, 7030~7035
- Lee DC, "Effects of Panax ginseng on tumor necrosis factor-α-mediated inflammation: a mini-review", Molecules, 16, pp.2802~2816 (2011)
- Paul S, "Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated from Korean ginseng (Panax ginseng C.A. Meyer)", Food Chem Toxicol, 50, pp.1354~1361 (2012)
- Vuksan V, "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, 18, pp.46~56 (2008)
- Hofseth LJ, "Inflammation, cancer, and targets of ginseng", J Nutr, 137(Suppl), pp.183S~185S (2007)
- Chun-Su Yuan, "Chemical and Pharmacological Studies of Saponins with a Focus on American Ginseng", Journal of Ginseng Research, 34(3), pp.160~167 (2010), 고려인삼학회
- Qi LW, "Metabolism of ginseng and its interactions with drugs", Curr Drug Metab, 12, pp.818~822 (2011)
- Chen Y, "Anti-cancer effects of ginsenoside compound k on pediatric acute myeloid leukemia cells", Cancer Cell Int, 13, pp.24~ (2013)
- Wang CZ, "Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma", Am J Chin Med, 39, pp.1161~1171 (2011)
- Song G, "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, 58, pp.12753~12760 (2010)
- Chae S, "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, 57, pp.5777~5782 (2009)
- 이강파, "The effect of yacon (Samallanthus sonchifolius) ethanol extract on cell proliferation and migration of C6 glioma cells stimulated with fetal bovine serum", Nutrition Research and Practice, 9(3), pp.256~261 (2015), 한국영양학회[DOI]
- Kobayashi T, "Matrix metalloproteinases-2 and -9 are secreted from human fibroblasts", Acta Derm Venereol, 83, pp.105~107 (2003)
- Chinot OL, "Response assessment criteria for glioblastoma: practical adaptation and implementation in clinical trials of antiangiogenic therapy", Curr Neurol Neurosci Rep, 13, pp.347~ (2013)
- Hess KR, "Adult glioma incidence trends in the United States, 1977-2000", Cancer, 101, pp.2293~2299 (2004)
- Paek IB, "Pharmacokinetics of a ginseng saponin metabolite compound K in rats", Biopharm Drug Dispos, 27, pp.39~45 (2006)
- Valenzuela-Fernández A, "Leukocyte elastase negatively regulates Stromal cell-derived factor-1 (SDF-1)", CXCR4 binding and functions by amino-terminal processing of SDF-1 and CXCR4, 2002, pp.277, 15677~15689
- Burger JA, "CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment", Blood, 107, pp.1761~1767 (2006)
- Hattermann K, "An infernal trio: the chemokine CXCL12and its receptors CXCR4 and CXCR7 in tumor biology", Ann Anat, 195, pp.103~110 (2013)
- Mukherjee D, "The role of chemokine receptor CXCR4 in breast cancer metastasis", Am J Cancer Res, 3, pp.46~57 (2013)
- Ehtesham M, "The role of the CXCR4 cell surface chemokine receptor in glioma biology", J Neurooncol, 113, pp.153~162 (2013)
- do Carmo A, "CXCL12", CXCR4 promotes motility and proliferation of glioma cells, 2010, pp.9, 56~65
- Jung SH, "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, 118, pp.490~497 (2006)
- Fang W, "Role of matrix metalloproteinases (MMPs) in tumor invasion and metastasis: serial studies on MMPs and TIMPs", Beijing Da Xue Xue Bao, 35, pp.441~443 (2003)
