黑色素瘤
上皮-间质转换
细胞凋亡
癌症研究
化学
程序性细胞死亡
下调和上调
生物
生物化学
基因
作者
Meng Wang,Shanshan Li,Youlin Wang,Hui Cheng,Jingjing Su,Qinglin Li
标识
DOI:10.1016/j.taap.2020.115110
摘要
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-β1-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-β1-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-β1-stimulated melanoma cells via the p53/SLC7A11/GPX4 signaling pathway.
科研通智能强力驱动
Strongly Powered by AbleSci AI