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Updated: Dec 26, 2025

Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research
Published on: March 29, 2024
Betulinic acid suppresses NGAL-induced epithelial-to-mesenchymal transition in melanoma
Dorina Gheorgheosu1, Michaela Jung, Bilge Ören
1Department of Pathophysiology, Victor Babes University of Medicine and Pharmacy, 300041 Timisoara, Romania.
Abstract:
Betulinic acid (BA) exhibits antitumoral activity by blocking proliferation, invasion, and angiogenesis. However, the impact of BA on epithelial-to-mesenchymal transition (EMT), a hallmark of cancer metastasis induced among others by neutrophil gelatinase-associated lipocalin (NGAL), remains unknown. The present study aimed at determining the effect of BA on NGAL-induced EMT. In A375 melanoma cells, BA downregulated mesenchymal markers, increased epithelial markers, and inhibited cytoskeletal reorganization. In addition, BA limited endogenous NGAL production and further suppressed EMT induced by exogenously added NGAL and the corresponding invasive cellular phenotype. In conclusion, BA interferes with EMT-associated changes, a mechanism to antagonize invasive melanoma cells.
Insights
Betulinic acid (BA) inhibits melanoma cell invasion by blocking epithelial-to-mesenchymal transition (EMT). This study shows BA reduces mesenchymal markers and suppresses NGAL-induced EMT, offering a potential therapeutic strategy.
Area of Science:
- Oncology
- Cancer Biology
- Molecular Medicine
Background:
- Betulinic acid (BA) demonstrates antitumoral properties, including inhibition of proliferation, invasion, and angiogenesis.
- Epithelial-to-mesenchymal transition (EMT) is a critical process in cancer metastasis.
- Neutrophil gelatinase-associated lipocalin (NGAL) is implicated in inducing EMT, but BA's effect on this process is unknown.
Purpose of the Study:
- To investigate the effect of Betulinic acid (BA) on NGAL-induced epithelial-to-mesenchymal transition (EMT) in melanoma cells.
- To determine if BA can reverse or inhibit the EMT process and associated invasive phenotypes.
Main Methods:
- A375 melanoma cells were treated with Betulinic acid (BA).
- Analysis included monitoring of epithelial and mesenchymal markers, cytoskeletal organization, and NGAL production.
- EMT was induced both endogenously and exogenously using NGAL.
Main Results:
- Betulinic acid (BA) downregulated mesenchymal markers and upregulated epithelial markers in A375 melanoma cells.
- BA inhibited cytoskeletal reorganization and limited endogenous NGAL production.
- BA suppressed NGAL-induced EMT and reduced the invasive cellular phenotype.
Conclusions:
- Betulinic acid (BA) interferes with EMT-associated changes in melanoma cells.
- BA antagonizes melanoma cell invasion by modulating EMT pathways.
- These findings suggest BA as a potential therapeutic agent against invasive melanoma.
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