Isobavachalcone’s Alleviation of Pyroptosis Contributes to Enhanced Apoptosis in Glioblastoma: Possible Involvement of NLRP3

Abstract Glioblastoma (GBM) is the worst and most common malignant intracranial tumor with high mortality rates and almost invariably poor prognosis even after surgery, radiotherapy, chemotherapy and emerging immunotherapies. Therefore, it is important to find new therapeutic drugs for GBM treatment. In the present study, we aimed to explore the effect of one natural chalcone—Isobavachalcone (IBC) on GBM and clarify its anti-cancer mechanisms. It was observed that IBC could inhibit GBM cell proliferation, migration and invasion in vitro and prevent tumor growth without any significant drug toxicity in vivo. Mechanistically, IBC may target NOD-like receptor family pyrin domain-containing 3 (NLRP3) transcription factor estrogen receptor 1 (ESR1) by network pharmacology and molecular docking analysis. Experimentally, IBC reduced NLRP3 inflammasome-related pyroptosis and inflammation, arrested cell cycle at G1 phase, and induced mitochondria-dependent apoptosis in GBM cells. These results indicated that IBC is a potential therapeutic drug against GBM and provide a new insight into GBM treatment.