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Gambogic acid exhibits anti-metastatic activity on malignant melanoma mainly through inhibition of PI3K/Akt and ERK signaling pathways.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2019 Dec 01; Vol. 864, pp. 172719. Date of Electronic Publication: 2019 Oct 03. - Publication Year :
- 2019
-
Abstract
- Gambogic acid (GA) is a potential anti-cancer compound that is extracted from the resin of Garciania hanburyi. The present study was designed to evaluate the anti-metastatic effect of GA on melanoma cell lines in vitro and to explore the underlying mechanism. The anti-proliferative activity of GA on melanoma cells was assessed by CCK-8 assay. The Wound-healing, transwell, adhesion, and tube formation assays were performed to examine the inhibition of GA on the cell's migration, invasion, adhesion, and angiogenesis capacities, respectively. Enzymatic activity of MMP-2 and MMP-9 were detected by gelatin zymography assay. Protein expressions regulated by GA treatment were tested by Western blot assay. The present results showed that GA significantly inhibited the proliferation of highly metastatic melanoma A375, B16-F10 cells and human umbilical vein endothelial cells (HUVECs) in time- and doses-dependent manners. Furthermore, GA significantly inhibited the migratory, invasive and adhesive properties of A375 and B16-F10 cells, and tube-forming potential of HUVECs at sub-IC <subscript>50</subscript> concentrations, where no significant cytotoxicity was observed. Mechanistically, GA treatment suppressed the EMT and angiogenesis processes and reduced the enzymatic activity of MMP-2 and MMP-9. Moreover, abnormal PI3K/Akt and ERK signaling pathways in A375 and B16-F10 cells and HUVECs were notably suppressed by GA treatment. Collectively, our results suggest that GA exerts anti-metastasis activity in melanoma cells by suppressing the EMT and angiogenesis through the PI3K/Akt and ERK signaling pathways, and might be used as a phytomedicine against metastatic melanoma.<br /> (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Line, Tumor
Cell Movement drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Humans
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Melanoma blood supply
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Neovascularization, Pathologic drug therapy
Skin Neoplasms blood supply
Vascular Endothelial Growth Factor A metabolism
Vascular Endothelial Growth Factor Receptor-2 metabolism
Xanthones therapeutic use
Melanoma, Cutaneous Malignant
Antineoplastic Agents pharmacology
Extracellular Signal-Regulated MAP Kinases metabolism
Melanoma pathology
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction drug effects
Skin Neoplasms pathology
Xanthones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0712
- Volume :
- 864
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31586634
- Full Text :
- https://doi.org/10.1016/j.ejphar.2019.172719