Ferroptosis Induction by Purple Sweet Potato Anthocyanins in T-cell Acute Lymphoblastic Leukemia: Combined Molecular Docking, In Vitro, and In Vivo Evidence

Background: Purple sweet potato anthocyanins (PSPAs), a class of dietary Flavonoids, have shown Anticancer potential. However, their ability to induce Ferroptosis in T-cell acute lymphoblastic leukemia (T-ALL) remains unexplored. This study aimed to investigate whether PSPAs can trigger Ferroptosis in T-ALL cells and to elucidate the underlying mechanisms.

Methods: Jurkat T-ALL cells were treated with PSPAs, and cell viability, Reactive Oxygen Species (ROS), lipid peroxidation, intracellular Fe²⁺, and expression of ferroptosis-related proteins (Glutathione Peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), nuclear factor erythroid 2-related factor 2 (Nrf2)) were assessed. Ferrostatin-1 was used to verify Ferroptosis involvement. Ultrastructural changes were examined by electron microscopy. Molecular docking was performed to evaluate PSPA binding to SLC7A11, and in vivo efficacy was tested in T-ALL xenograft mice.

Results: PSPAs exhibited significant cytotoxicity in Jurkat cells, which was reversed by ferrostatin-1, indicating Ferroptosis involvement. Treatment elevated ROS and lipid peroxidation, increased intracellular Fe²⁺, and downregulated GPX4 and SLC7A11 without altering Nrf2, suggesting that SLC7A11 may be directly targeted. Electron microscopy revealed hallmark ferroptotic changes, including increased mitochondrial membrane density, loss of cristae, and rupture of the outer membrane. Molecular docking demonstrated strong binding of four PSPA components to multiple residues of SLC7A11, including Cys158, a key functional site. In vivo, PSPAs markedly inhibited tumor growth in T-ALL xenograft mice, achieving up to 75% suppression, as evidenced by histological analysis showing disrupted tumor architecture and cell membrane rupture.

Conclusions: This study provides the first evidence that PSPAs induce Ferroptosis in T-ALL through modulation of the SLC7A11/GPX4 pathway. These findings reveal new mechanistic insights into Ferroptosis in T-ALL and highlight PSPAs as safe, naturally derived therapeutic agents with promising therapeutic potential for leukemia.

amino acid transport system Xc–; anthocyanins; ferroptosis; glutathione peroxidase 4; leukemia.