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Betulinic acid suppresses NGAL-induced epithelial-to-mesenchymal transition in melanoma.

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.
AuthorsDorina Gheorgheosu, Michaela Jung, Bilge Ören, Tobias Schmid, Cristina Dehelean, Danina Muntean, Bernhard Brüne
JournalBiological chemistry (Biol Chem) Vol. 394 Issue 6 Pg. 773-81 (Jun 2013) ISSN: 1437-4315 [Electronic] Germany
PMID23399635 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Pentacyclic Triterpenes
  • Proto-Oncogene Proteins
  • Triterpenes
  • Betulinic Acid
Topics
  • Acute-Phase Proteins (metabolism)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Epithelial Cells (drug effects, metabolism, pathology)
  • Epithelial-Mesenchymal Transition (drug effects)
  • Humans
  • Lipocalin-2
  • Lipocalins (metabolism)
  • Melanoma (pathology)
  • Neoplasm Invasiveness
  • Pentacyclic Triterpenes
  • Phenotype
  • Proto-Oncogene Proteins (metabolism)
  • Triterpenes (chemistry, pharmacology)
  • Betulinic Acid

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