Abstract
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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No datasets were generated or analysed during the current study.
Abbreviations
- BSA:
-
Bovine serum albumin
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DMSO:
-
Dimethyl sulfoxide
- ECM:
-
Extracellular matrix
- EMT:
-
Epithelial-mesenchymal transition
- FBS:
-
Fetal bovine serum
- GBA:
-
Galbanic acid
- MMPs:
-
Matrix metalloproteinases
- PBS:
-
Phosphate-buffered saline
- PFA:
-
Paraformaldehyde
- qRT-PCR:
-
Quantitative reverse transcription-polymerase chain reaction
- SDS:
-
Sodium dodecyl sulfate
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Acknowledgements
This research was financially supported by a research grant (Grant number: 4001585) from the Vice Chancellor of Research of Mashhad University of Medical Sciences, Mashhad, Iran and the Vice-Chancellor for Research and Technology of Ferdowsi University of Mashhad, Mashhad, Iran. The results described in this paper were part of a M.Sc. thesis.
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This research was financially supported by a research grant (Grant number: 4001585) from the Vice Chancellor of Research of Mashhad University of Medical Sciences, Mashhad, Iran, and Ferdowsi University of Mashhad, Mashhad, Iran.
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M.A. and F.H. carried out the experiments, wrote the manuscript, and designed the figures. H.H. and S.G performed part of the experiments. E. M. co-wrote the paper. F. R. and K. J. conceived the original idea and supervised the project. All authors contributed to the final manuscript. The authors declare that all data were generated in-house. The authors declare that all data were generated in-house and that no paper mill was used.
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The results described in this paper were part of a M.Sc. thesis.
Masoumeh Azad and Fatemehsadat Hosseini contributed equally to this work.
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Azad, M., Hosseini, F., Hassanzade, H. et al. Galbanic acid suppresses melanoma cell migration and invasion by reducing MMP activity and downregulating N-cadherin and fibronectin. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-02981-4
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DOI: https://doi.org/10.1007/s00210-024-02981-4