Novel curcumin derivative DMC-GF suppresses glioblastoma growth by targeting MAPK1 and TRIM21 to modulates STAT3/AKT phosphorylation

Glioblastoma multiforme (GBM) remains a therapeutic challenge with a poor prognosis, necessitating novel treatment strategies. This study investigated the anti-tumor efficacy of a novel demethoxycurcumin derivative, DMC-GF, against GBM. Both in vitro assays and an orthotopic xenograft model demonstrated that DMC-GF significantly suppressed GBM cell proliferation, induced apoptosis, and potently inhibited tumor growth in vivo. Mechanistically, DMC-GF was found to target MAPK1 and interact with TRIM21, thereby modulating the phosphorylation of the STAT3/AKT signaling axis and triggering the mitochondrial apoptotic pathway. Furthermore, integrated metabolomic and transcriptomic analyses identified the regulation of mitochondrial oxidative phosphorylation as a central event in the therapeutic mechanism of DMC-GF. In conclusion, DMC-GF exerts its anti-glioblastoma effects primarily by inducing mitochondrial apoptosis via suppression of the phosphorylated STAT3/AKT pathway, positioning it as a promising therapeutic candidate.