Selenium nanoparticles decorated by fucoidan induce ferroptosis in HepG2 cells.

Unlike apoptosis, necrosis and autophagy, ferroptosis is a novel type of regulated cell death, and the mechanism by which selenium nanoparticles induce ferroptosis in cancer cells has rarely been investigated. To investigate the mechanism of inhibition of HepG2 cell proliferation by fucoidan-selenium nanoparticles (FD-SeNPs) by inducing ferroptosis. The mechanism was explored by detecting ROS, MDA, GSH and Fe and utilizing TEM and Western blot assay. The results showed that FD-SeNPs increased intracellular ROS, MDA and Fe levels and decreased GSH levels. Moreover, HepG2 cells treated with FD-SeNPs showed mitochondrial shrinkage, volume reduction and mitochondrial cristae breakage. The ability to reverse the changes in the above indexes after Ferrostatin-1 (Fer-1) intervention suggests that FD-SeNPs inhibit HepG2 cell proliferation by inducing cells to undergo ferroptosis. Further mechanistic studies revealed that FD-SeNPs decreased the expression of Nrf2, HO-1, SLC7A11 (xCT), GCLC and GPX4 proteins to promote lipid peroxidation in HepG2 cells. Moreover, FD-SeNPs could disrupt intracellular iron homeostasis by up-regulating transferrin protein and down-regulating SLC40A1 and Ferritin proteins, suggesting that FD-SeNPs induced cells to undergo ferroptosis by regulating proteins related to lipid peroxidation and iron homeostasis. This study provides theoretical data for reference in applying FD-SeNPs in developing anti-cancer clinical drugs.