Borax regulates iron chaperone‐ and autophagy‐mediated ferroptosis pathway in glioblastoma cells

Abstract

AbstractGlioblastoma (GBM) is classified as a stage‐IV glioma. Unfortunately, there are currently no curative treatments for GBM. Poly(rC)‐binding protein 1 (PCBP1) is a cytosolic iron chaperone with diverse functions. PCBP1 is also known to regulate autophagy, but the role of PCBP1 in ferroptosis, iron‐dependent cell death pathway, remains unrevealed in GBM cells. Here, we investigated the effects of borax, a boron compound, on the ferroptosis signaling pathway mediated by PCBP1 and autophagy. The study analyzed cell viability, proliferation, and cell cycle on U87‐MG and HMC3 cells to investigate the effects of borax. After determining the cytotoxic concentrations of borax, morphological analyzes and measurement of PCBP1, Beclin1, malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPx4) and acyl‐CoA synthetase long chain family member 4 (ACSL4) levels were performed. Finally, expression levels of PCBP1, Beclin1, GPx4 and ACSL4, and caspase‐3/7 activity were determined. We found that borax reduced U87‐MG cell viability in a concentration‐ and time‐dependent manner. Additionally, borax altered cell proliferation and remarkably reduced S phase in the U87‐MG cells and exhibited selectivity by having an opposite effect on normal cells (HMC3). According to DAPI staining, borax caused nuclear deficits in U87‐MG cells. The result showed that borax in U87‐MG cells induced reduction of the PCBP1, GSH, and GPx4 and enhancement of Beclin1, MDA, and ACSL4. Furthermore, borax triggered apoptosis by activating caspase 3/7 in U87‐MG cells. Our study indicated that the borax has potential as an anticancer treatment for GBM via regulating PCBP1/Beclin1/GPx4/ACSL4 signaling pathways.