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Fucoxanthin triggers ferroptosis in glioblastoma cells by stabilizing the transferrin receptor. 2023

Qin Zhu, and Yanqing Zhou, and Haixia Wang, and Tao Cao, and Xinzhi Wang, and Rui Liu, and Hao Wu, and Binyan Lin
Experiment Center of Science and Technology, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

Glioblastoma (GBM) is the most common and lethal tumor in the world, possessing high stemness, aggressiveness and resistance. Fucoxanthin is a bio-active compound extracted from seaweeds that shows anti-tumor effects to different types of tumors. Here, we show that fucoxanthin inhibits the survival of GBM cells by triggering ferroptosis, a ferric ion and reactive oxygen species (ROS) dependent cell death and ferrostatin-1 could block it. Furthermore, we identified that fucoxanthin targets the transferrin receptor (TFRC). Fucoxanthin is able to block degradation and maintain high levels of TFRC, and similarly inhibits the growth of GBM xenografts in vivo, downregulates the expression of proliferating cell nuclear antigen (PCNA) and upregulates the levels of TFRC in tumor tissues. In conclusion, we demonstrate that fucoxanthin has a significant anti-GBM effect by triggering ferroptosis.

UI MeSH Term Description Entries
D011990 Receptors, Transferrin Membrane glycoproteins found in high concentrations on iron-utilizing cells. They specifically bind iron-bearing transferrin, are endocytosed with its ligand and then returned to the cell surface where transferrin without its iron is released. Transferrin Receptors,Transferrin Receptor,Receptor, Transferrin
D005909 Glioblastoma A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000079403 Ferroptosis A form of REGULATED CELL DEATH initiated by oxidative perturbations of the intracellular microenvironment that is under constitutive control by glutathione peroxidase 4 and can be inhibited by iron chelators and lipophilic antioxidants. Oxytosis
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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