Gambogenic acid induces ferroptosis in melanoma cells undergoing epithelial-to-mesenchymal transition.
Toxicol Appl Pharmacol
; 401: 115110, 2020 08 15.
Article
en En
| MEDLINE
| ID: mdl-32533954
ABSTRACT
Melanoma is characterized by high malignancy and early onset of metastasis. Epithelial-to-mesenchymal transition (EMT) is an early event during tumor metastasis. Tumor cells that develop EMT can escape apoptosis, but they are vulnerable to ferroptosis inducers. Gambogenic acid (GNA), a xanthone found in Gamboge, has cytotoxic effects in highly invasive melanoma cells. This study investigated the anti-melanoma effect and mechanism of action of GNA in TGF-ß1-induced EMT melanoma cells. We found that GNA significantly inhibited the invasion, migration and EMT in melanoma cells, and these cells exhibited small mitochondrial wrinkling (an important feature of ferroptosis). An iron chelator, but not an apoptosis inhibitor or a necrosis inhibitor, abolished the inhibitory effects of GNA on proliferation, invasion and migration of TGF-ß1-stimulated melanoma cells. GNA upregulated the expression of p53, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in the model cells, contributing to the mechanisms underlying GNA-induced ferroptosis. Collectively, our findings suggest that GNA induces ferroptosis in TGF-ß1-stimulated melanoma cells via the p53/SLC7A11/GPX4 signaling pathway.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Cutáneas
/
Xantenos
/
Medicamentos Herbarios Chinos
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Transición Epitelial-Mesenquimal
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Ferroptosis
/
Melanoma
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Año:
2020
Tipo del documento:
Article