Piperlongumine inhibits glioblastoma proliferation by inducing ferroptosis

Abstract Objectives This study aimed to investigate the effects of Piperlongumine on Glioblastoma multiforme. Methods The effects of Piperlongumine on the viability and proliferation of glioma cells LN229 and A172 were measured. Changes in mitochondrial structure were observed. Cell proliferative capacity was assessed using immunofluorescence. The levels of glutathione, malondialdehyde, 4-hydroxynonenal, and intracellular reactive oxygen species were detected. The levels of ferroptosis-related proteins were detected. A plasmid transfection was performed to overexpress the nuclear factor erythroid 2-related factor 2 gene; a subcutaneous tumor model was established in nude mice to observe the in vivo inhibitory effects of Piperlongumine on Glioblastoma multiforme and the recovery effect of Fer-1. The expression levels of ferroptosis-related proteins were detected using immunohistochemistry. Key findings Piperlongumine inhibited the viability of glioma cells, as well as their proliferation. The ferroptosis inhibitors were able to restore the inhibitory effect of Piperlongumine on glioma cell proliferation. Forced overexpression of nuclear factor erythroid 2-related factor 2 partially reversed Piperlongumine-induced ferroptosis; Piperlongumine exhibited a significant inhibitory effect on Glioblastoma multiforme cells in vivo, which could be restored by Fer-1. Conclusions Piperlongumine inhibits Glioblastoma multiforme proliferation by inducing ferroptosis in vitro and vivo model.