Mechanism of Fucoxanthin on Ferroptosis of Human Erythroleukemia Cells Via the TFR1/SLC7A11/GPX4 Signaling Pathway
DOI:
https://doi.org/10.53469/jcmp.2025.07(01).38Keywords:
Fucoxanthin, Human erythroleukemia cell, Ferroptosis, Reactive oxygen species, Cell cycle, TFR1/SLC7A11/GPX4 signaling pathwayAbstract
Background: Fucoxanthin (Fx) is a natural carotenoid gaining widespread interest for its anticancer effects. However, the mechanism by which Fx treats leukemia remains unclear. Here, we studied the mechanism of Fx-induced ferroptosis in human erythroleukemia (HEL) cells. Methods: HEL cell viability after Fx treatment was assessed using an MTT assay. Mitochondrial membrane potential (MMP) and cell cycle distribution of HEL cells were determined using flow cytometry. Fucoxanthin's effect on reactive oxygen species (ROS), iron and ferrous ions in HEL cells was measured using assay kits. Expression levels of relevant proteins in HEL cells were assessed through western blot analysis. Molecular docking was performed to validate the interactions. Results: Fx significantly inhibited HEL cell viability both dose- and time-dependently. As the Fx concentration increased, the proportion of cells in the G0/G1 phase significantly increased, and MMP and cells in the S phase were notably decreased. Fx markedly promoted ROS, iron and ferrous ion expression levels; reduced GPX4 and SCL7A11 expression levels, and increased p53 and TFR1 expression levels. Molecular docking analysis revealed that the binding energy between Fx and GPX4, SCL7A11, p53 and TFR1 was less than −5 kcal/mol, primarily through hydrogen bonding at the enzyme's active site. Conclusion: Fx-induced ferroptosis of HEL cells may be related to activation of the TFR1/SLC7A11/GPX4 signaling pathway.
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Copyright (c) 2025 Bi Wang, Siyu Wang, Haofei Du, Ziyan Yang, Xiuqiang Zhang, Caisheng Wang, Haomiao Ding
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