GluOC Induced SLC7A11 and SLC38A1 to Activate Redox Processes and Resist Ferroptosis in TNBC

Ferroptosis, a type of programmed cell death, is mainly associated with disruptions in iron metabolism, imbalances in the amino acid antioxidant system, and the build-up of lipid peroxides. Triple-negative breast cancer (TNBC) has a dismal prognosis. Since activating ferroptosis can suppress breast cancer cell proliferation, it holds promise as a novel therapeutic target for breast cancer patients. Thus, the objective of this study was to clarify the mechanism of ferroptosis in TNBC, aiming to find new treatment strategies for TNBC patients.

We screened out the differential genes related to ferroptosis in TNBC after GluOC treatment based on the whole-genome sequencing results. At the cellular level, we conducted explorations using techniques such as quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, fluorescence staining, and siRNA transfection. Moreover, we further verified the role of GluOC in inhibiting ferroptosis in TNBC through in vivo experiments using nude mice.

The results showed that GluOC enhanced glutathione expression levels by inducing SLC7A11 accumulation via the specific signaling pathway. Additionally, GluOC increased ATP production and tricarboxylic acid flux resistance to ferroptosis through SLC38A1. Overall, GluOC coordinately regulated SLC7A11 and SLC38A1 to inhibit ferroptosis in TNBC.

This study elucidated the mechanism of GluOC in inhibiting ferroptosis in TNBC. The findings not only provided new insights into ferroptosis but also potentially offered new concepts for the development of future anticancer therapies, which may contribute to improving the treatment of TNBC patients.