Scutellarin Nanoparticles Inhibit Colon Cancer by Regulating Ferroptosis

Background In our previous research, we addressed the issues of poor stability and water solubility of scutellarin by developing scutellarin nanoparticles. Our findings indicated that these nanoparticles exhibited enhanced anti-colon cancer activity compared to scutellarin alone. However, the underlying mechanisms of scutellarin’s anti-colon cancer effects require further investigation. Scutellarin is known to suppress the proliferation of different tumor cells. In this study, we explored whether scutellarin, encapsulated in nanoparticles, could suppress the proliferation of colon cancer cells by modulating ferroptosis. Objectives In this study, we explored whether scutellarin, encapsulated in nanoparticles, could suppress the proliferation of colon cancer cells by modulating ferroptosis. Materials and Methods SW480 and HCT-116 cells were divided into (a) control group, scutellarin group, and scutellarin nanoparticles group; and (b) control group, scutellarin nanoparticles group, ferrostatin-1 group, and scutellarin nanoparticles + ferrostatin-1 group. First, we determined the half-maximal inhibitory concentration of colon cancer cells by Cell Counting Kit-8 (CCK-8) assay. Then, the ferroptosis of cells in each group was detected, and the levels of oxidative stress-related factors, superoxide dismutase (SOD) and malondialdehyde (MDA), were detected by biochemical kits. Cell death was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, cell invasion was detected by Transwell assay, and reactive oxygen species (ROS) levels were detected by flow cytometry. Western blotting was used to detect ferroptosis-related glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroportin 1 (FPN1) expression levels. Results We found that in SW480 and HCT-116 cells, the IC50 of scutellarin nanoparticles cells was lower, cell apoptosis and invasion were more obvious, the oxidative stress level was also higher, Fe 2+ content was increased, and the expression of GPX4, SLC7A11, and FPN1 was decreased. These results were changed after the addition of ferrostatin-1. Conclusion Scutellarin nanoparticles have a better anti-tumor effect than the same dose of scutellarin. Scutellarin nanoparticles can inhibit the proliferation, migration, and invasion of cancer cells by promoting ferroptosis, as well as cell apoptosis.