Gambogic acid exhibits anti-metastatic activity on malignant melanoma mainly through inhibition of PI3K/Akt and ERK signaling pathways.

Gambogic acid exhibits anti-metastatic activity on malignant melanoma mainly through inhibition of PI3K/Akt and ERK signaling pathways.

Publication date: Oct 03, 2019

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 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.

Li, C.Y., Wang, Q., Wang, X.M., Li, G.X., Shen, S., and Wei, X.L. Gambogic acid exhibits anti-metastatic activity on malignant melanoma mainly through inhibition of PI3K/Akt and ERK signaling pathways. 24376. 2019 Eur J Pharmacol.

Concepts Keywords
Acid Anti metastatic melanoma
Adhesion Branches of biology
Adhesive Enzymes
Akt Medical specialties
Angiogenesis Oncology
Assay Signal transduction
Cancer Cancer research
Cytotoxicity C-Met
EMT MTOR
Endothelial Epithelial–mesenchymal transition
Enzymatic Metastasis
ERK Phosphoinositide 3-kinase
Gelatin Melanoma
Malignant Melanoma
Melanoma
Metastasis
Metastatic
Migratory
MMP
Phytomedicine
PI3K
Resin
Umbilical Vein
Western Blot
Wound Healing

Semantics

Type Source Name
disease MESH metastasis
gene UNIPROT SLC22A3
gene UNIPROT ITK
gene UNIPROT TUBE1
gene UNIPROT GKN2
drug DRUGBANK Gelatin
gene UNIPROT MMP9
gene UNIPROT MMP2
pathway BSID Angiogenesis
drug DRUGBANK Sincalide
pathway BSID Melanoma
disease DOID cancer
disease MESH cancer
gene UNIPROT EPHB2
disease DOID malignant melanoma
disease MESH malignant melanoma

Original Article

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