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Galbanic Acid Suppresses Melanoma Cell Migration and Invasion by Reducing MMP Activity and Downregulating N-cadherin and Fibronectin.

Masoumeh Azad,Fatemehsadat Hosseini, Halimeh Hassanzade, Shahin Gharedaghi,Elahe Mahdipour,Fatemeh B. Rassouli,Khadijeh Jamialahmadi

Naunyn-Schmiedeberg's archives of pharmacology(2024)

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摘要
High mortality rate of melanoma is due to the metastasis of malignant cells. Galbanic acid (GBA) is a natural sesquiterpene coumarin with valuable pharmaceutical activities. Our study aimed to investigate whether GBA can affect the migration, invasion, and adhesion of melanoma cells. The survival rate of B16F10 cells was measured using the alamarBlue assay. Scratch, adhesion, and invasion assays were performed to determine the effect of GBA on metastatic behavior of cells. Moreover, gelatin zymography was done to assess the activity of MMP-2 and MMP-9, and qRT-PCR was used to investigate the effect of GBA on the expression of candidate genes. Based on the results of alamarBlue assay, 40 µM GBA was chosen as the optimum concentration for all tests. Our findings indicated that GBA significantly decreased the invasion and migration of B16F10 cells while enhancing their adhesion ability. In addition, gelatin zymography demonstrated that GBA reduced the enzymatic activity of MMP-2 and MMP-9. Moreover, qRT-PCR revealed that GBA reduced the expression of N-cadherin and fibronectin. Current findings demonstrated, for the first time, that GBA inhibited the migration and invasion of melanoma cells via reducing the activity of MMP-2 and MMP-9 and downregulating N-cadherin and fibronectin expression. Accordingly, GBA could be suggested as a potential therapeutic agent for the treatment of melanoma.
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关键词
Galbanic acid,Gene expression,Invasion,Matrix metalloproteinase,Melanoma,Metastasis,Migration
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