Anti-Metastasis Effects of Ginsenoside Rg3 in B16F10 Cells
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초록
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.
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.
참고문헌 (28)
- Boregowda RK, "RUNX2 is overexpressed in melanoma cells and mediates their migration and invasion", Cancer Lett, 348, pp.61~70 (2014)
- Chalkiadaki G, "Heparin plays a key regulatory role via a p53", FAK-dependent signaling in melanoma cell adhesion and migration, 2011, pp.63, 109~119
- Chen D, "1,25-Dihydroxyvitamin D3 activates MMP13 gene expression in chondrocytes through p38 MARK pathway", Int. J. Biol. Sci, 9, pp.649~655 (2013)
- Chen Y, "Shikonin inhibits prostate cancer cells metastasis by reducing matrix metalloproteinase-2", -9 expression via AKT, ERK1, pp.2 pathways, Int. Immunopharmacol[DOI]
- Chiang HM, "Fisetin ameliorated photodamage by suppressing the MAP kinase", MMP pathway and NF-kappaB pathways, 2015, ~
- Jeong YJ, "Melittin suppresses EGF-induced cell motility and invasion by inhibiting PI3K", Akt, Food Chem. Toxicol, pp.2014, 68[DOI]
- Jia D, "Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion", BMC Cancer, 10, pp.364~ (2010)
- Jimenez RE, "Effect of matrix metalloproteinase inhibition on pancreatic cancer invasion and metastasis: an additive strategy for cancer control", Ann. Surg, 231, pp.644~654 (2000)
- Ji Seong Kim, "Induction of Apoptosis by Ginsenoside Rk1 in SK-MEL-2-Human Melanoma", Archives of Pharmacal Research, 35(4), pp.717~722 (2012), 대한약학회[DOI]
- Kim JW, "Ginsenoside Rg3 attenuates tumor angiogenesis via inhibiting bioactivities of endothelial progenitor cells", Cancer Biol. Ther, 13, pp.504~515 (2012)
- Kim SM, "Combination of ginsenoside Rg3 with docetaxel enhances the susceptibility of prostate cancer cells via inhibition of NF-kappaB", Eur. J. Pharmacol, 631, pp.1~9 (2010)
- Kim YJ, "Stereospecific effects of ginsenoside 20-Rg3 inhibits TGF-beta1-induced epithelial-mesenchymal transition and suppresses lung cancer migration, invasion and anoikis resistance", Toxicology, 322, pp.23~33 (2014)
- Ko SY, "Cell migration is regulated by AGE-RAGE interaction in human oral cancer cells in vitro", PLoS One, 9, pp.e110542~ (2014)
- Lecomte J, "Bone marrow-derived myofibroblasts are the providers of pro-invasive matrix metalloproteinase 13 in primary tumor", Neoplasia, 14, pp.943~951 (2012)
- 이슬기, "ginsenoside Rg3에 의한 B16F10 흑색종 세포의 세포사멸 유도", 생명과학회지, 24(9), pp.1001~1005 (2014), 한국생명과학회
- Meierjohann S, "MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation", Mol. Cancer, 9, pp.201~ (2010)
- Ozawa H, "Sulfatides inhibit adhesion, migration, and invasion of murine melanoma B16F10 cell line in vitro", Biol. Pharm. Bull, 35, pp.2054~2058 (2012)
- Pivetta E, "MMP-13 stimulates osteoclast differentiation and activation in tumour breast bone metastases", Breast Cancer Res, 13, pp.R105~ (2011)
- Song Y, "Blueberry peel extracts inhibit adipogenesis in 3T3-L1cells and reduce high-fat diet-induced obesity", PLoS One, 8, pp.e69925~ (2013)
- Tsai HE, "Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma", PLoS One, 8, pp.e59345~ (2013)
- Wang Z, "Baicalein induces apoptosis and autophagy via endoplasmic reticulum stress in hepatocellular carcinoma cells", 732516~ (2014)
- Westermarck J, "Regulation of matrix metalloproteinase expression in tumor invasion", FASEB J, 13, pp.781~792 (1999)
- Xu TM, "Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis", Chin. Med. J. (Engl.), 121, pp.1394~1397 (2008)
- Yamada T, "Overexpression of MMP-13 gene in colorectal cancer with liver metastasis", Anticancer Res, 30, pp.2693~2699 (2010)
- Yong HY, "The p38 MAPK inhibitors for the treatment of inflammatory diseases and cancer", Exp. Opin. Invest. Drugs, 18, pp.1893~1905 (2009)
- Zehavi L, "MiR-377 targets E2F3 and alters the NF-kB signaling pathway through MAP3K7 in malignant melanoma", Mol. Cancer, 14, pp.68~ (2015)
- Zhang P, "Cordycepin (3'-deoxyadenosine) suppressed HMGA2, Twist1and ZEB1-dependent melanoma invasion and metastasis by targeting miR-33b", Oncotarget, 6, pp.9834~9853 (2015)
- Zhao X, "An animal model of buccal mucosa cancer and cervical lymph node metastasis induced by U14 squamous cell carcinoma cells", Exp. Ther. Med, 5, pp.1083~1088 (2013)