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http://dx.doi.org/10.4014/jmb.1506.06002

Anti-Metastasis Effects of Ginsenoside Rg3 in B16F10 Cells  

Lee, Seul Gi (Department of Food Engineering, Kyungpook National University)
Kang, Young Jin (Department of Pharmacology, College of Medicine, Yeungnam University)
Nam, Ju-Ock (Department of Food Engineering, Kyungpook National University)
Publication Information
Journal of Microbiology and Biotechnology / v.25, no.12, 2015 , pp. 1997-2006 More about this Journal
Abstract
Ginsenoside Rg3 is a bioactive ginseng constituent that has been reported to have diverse pathological and physiological effects, including anti-inflammatory and anti-metastatic activities. Metastasis is one of the most important factors involved in patients with melanoma. However, the molecular mechanism underlying the anti-metastatic activities of Rg3 in malignant melanoma cancer has not been fully elucidated. In this study, we have evaluated that Rg3 effectively inhibits metastasis of B16F10 melanoma cancer cells. We found that Rg3 significantly suppresses the migration, invasion, wound healing, and colony-forming abilities of B16F10 cells in a dose-dependent manner. Mechanistically, we demonstrate that Rg3 suppresses B16F10 cell metastasis by inhibiting MMP-13 expression. These results indicate that Rg3 suppresses the metastasis of B16F10 mouse melanoma cancer cells via MMP-13 regulation. Importantly, MMP-13 downregulation may influence the migration and invasion capabilities of melanoma cells and has been correlated with melanoma progression. Therefore, Rg3 is a potential therapeutic candidate that could be used to treat patients with metastatic melanoma.
Keywords
B16F10; cancer; migration; ginsenoside Rg3; MMP-13; metastasis;
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1 Lee SG, Kim BS, Nam J-O. 2014. Ginsenoside Rg3 induces apoptosis in B16F10 melanoma cells. Kor. J. Life Sci. 24: 1001-1009.   DOI
2 Lecomte J, Masset A, Blacher S, Maertens L, Gothot A, Delgaudine M, et al. 2012. Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor. Neoplasia 14: 943-951.   DOI
3 Ko SY, Ko HA, Shieh TM, Chang WC, Chen HI, Chang SS, Lin IH. 2014. Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro. PLoS One 9: e110542.   DOI
4 Kim YJ, Choi WI, Jeon BN, Choi KC, Kim K, Kim TJ, et al. 2014. Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-beta1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance. Toxicology 322: 23-33.   DOI
5 Kim SM, Lee SY, Cho JS, Son SM, Choi SS, Yun YP, et al. 2010. Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB. Eur. J. Pharmacol. 631: 1-9.   DOI
6 Zhang P, Huang C, Fu C, Tian Y, Hu Y, Wang B, et al. 2015. Cordycepin (3'-deoxyadenosine) suppressed HMGA2, Twist1 and ZEB1-dependent melanoma invasion and metastasis by targeting miR-33b. Oncotarget 6: 9834-9853.   DOI
7 Zehavi L, Schayek H, Jacob-Hirsch J, Sidi Y, Leibowitz-Amit R, Avni D. 2015. MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma. Mol. Cancer 14: 68.   DOI
8 Yong HY, Koh MS, Moon A. 2009. The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer. Exp. Opin. Invest. Drugs 18: 1893-1905.   DOI
9 Yamada T, Oshima T, Yoshihara K, Tamura S, Kanazawa A, Inagaki D, et al. 2010. Overexpression of MMP-13 gene in colorectal cancer with liver metastasis. Anticancer Res. 30: 2693-2699.
10 Xu TM, Cui MH, Xin Y, Gu LP, Jiang X, Su MM, et al. 2008. Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis. Chin. Med. J. (Engl.) 121: 1394-1397.
11 Westermarck J, Kahari VM. 1999. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J. 13: 781-792.   DOI
12 Wang Z, Jiang C, Chen W. 2014. Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma cells. 2014: 732516.
13 Tsai HE, Wu JC, Kung ML, Liu LF, Kuo LH, Kuo HM, et al. 2013. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected]. PLoS One 8: e59345.   DOI
14 Song Y, Park HJ, Kang SN, Jang SH, Lee SJ, Ko YG, et al. 2013. Blueberry peel extracts inhibit adipogenesis in 3T3-L1 cells and reduce high-fat diet-induced obesity. PLoS One 8: e69925.   DOI
15 Zhao X, Pang L, Qian Y, Wang Q, Li Y, Wu M, et al. 2013. An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells. Exp. Ther. Med. 5: 1083-1088.   DOI
16 Kim JS, Joo EJ, Chun J, Ha YW, Lee JH, Han Y, Kim YS. 2012. Induction of apoptosis by ginsenoside Rk1 in SK-MEL-2-human melanoma. Arch. Pharm. Res. 35: 717-722.   DOI
17 Chalkiadaki G, Nikitovic D, Berdiaki A, Katonis P, Karamanos NK, Tzanakakis GN. 2011. Heparin plays a key regulatory role via a p53/FAK-dependent signaling in melanoma cell adhesion and migration. IUBMB Life 63: 109-119.
18 Boregowda RK, Olabisi OO, Abushahba W, Jeong BS, Haenssen KK, Chen W, et al. 2014. RUNX2 is overexpressed in melanoma cells and mediates their migration and invasion. Cancer Lett. 348: 61-70.   DOI
19 Kim JW, Jung SY, Kwon YH, Lee JH, Lee YM, Lee BY, Kwon SM. 2012. Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells. Cancer Biol. Ther. 13: 504-515.   DOI
20 Jimenez RE, Hartwig W, Antoniu BA, Compton CC, Warshaw AL, Fernandez-Del Castillo C. 2000. Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control. Ann. Surg. 231: 644-654.   DOI
21 Chen Y, Zheng L, Liu J, Zhou Z, Cao X, Lv X, Chen F. 2014. Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2/-9 expression via AKT/mTOR and ROS/ERK1/2 pathways. Int. Immunopharmacol. 21: 447-455.   DOI
22 Jia D, Yan M, Wang X, Hao X, Liang L, Liu L, et al. 2010. Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion. BMC Cancer 10: 364.   DOI
23 Jeong YJ, Choi Y, Shin JM, Cho HJ, Kang JH, Park KK, et al. 2014. Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K/Akt/mTOR signaling pathway in breast cancer cells. Food Chem. Toxicol. 68: 218-225.   DOI
24 Chiang HM, Chan SY, Chu Y, Wen KC. 2015. Fisetin ameliorated photodamage by suppressing the MAP kinase/MMP pathway and NF-kappaB pathways. J. Agric. Food Chem.
25 Chen D, Li Y, Dai X, Zhou X, Tian W, Zhou Y, et al. 2013. 1,25-Dihydroxyvitamin D3 activates MMP13 gene expression in chondrocytes through p38 MARK pathway. Int. J. Biol. Sci. 9: 649-655.   DOI
26 Pivetta E, Scapolan M, Pecolo M, Wassermann B, Abu-Rumeileh I, Balestreri L, et al. 2011. MMP-13 stimulates osteoclast differentiation and activation in tumour breast bone metastases. Breast Cancer Res. 13: R105.   DOI
27 Ozawa H, Sonoda Y, Kato S, Suzuki E, Matsuoka R, Kanaya T, et al. 2012. Sulfatides inhibit adhesion, migration, and invasion of murine melanoma B16F10 cell line in vitro. Biol. Pharm. Bull. 35: 2054-2058.   DOI
28 Meierjohann S, Hufnagel A, Wende E, Kleinschmidt MA, Wolf K, Friedl P, et al. 2010. MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation. Mol. Cancer 9: 201.   DOI