Morus alba L. (white mulberry) is a medicinal plant whose extracts possess significant anti-tumor potential.Through screening 59 commercially available mulberry-derived compounds, we identified a small molecule, Sanggenol L (SL), which exhibited potent inhibitory effects on glioblastoma while showing minimal toxicity toward normal cells.This study aimed to elucidate the anti-cancer function and underlying mechanism of SL in glioblastoma cells.Experimental results demonstrated that SL induced cytotoxic endoplasmic reticulum (ER) stress, suppressed cell viability, and triggered apoptosis.Mechanistically, LC-MS/MS and CETSA analyses revealed that SL specifically binds to BiP, creating a steric hindrance that blocks its interaction with IRE1.This leads to excessive dimerization of IRE1 and hyper-activation of the IRE1/CHOP/XBP1s/Bcl-2 pathway, thereby amplifying cytotoxic ER stress and ultimately promoting apoptosis.Furthermore, we found that SL promotes ubiquitination and degradation of MGMT, consequently enhancing the chemosensitivity of glioblastoma to temozolomide.
Xu et al. (Thu,) studied this question.