Curcumin induces apoptosis in osteosarcoma cells by regulating the glycolytic pathway via the MAPK axis: a mechanistic study

Abstract This study investigated the mechanism by which curcumin induces apoptosis through glycolytic regulation in osteosarcoma cells (U2OS, MG63) via the MAPK axis. Network pharmacology, protein-protein interaction analysis, and molecular docking were integrated to identify core targets and validate the central role of the MAPK pathway. In vitro , curcumin dose-dependently inhibited cell proliferation (IC50: 32.6 μmol/L in MG63, 37.3 μmol/L in U2OS) and migration, while promoting apoptosis as confirmed by CCK-8, wound healing, flow cytometry, and TUNEL assays. Western blot analysis demonstrated that curcumin significantly upregulated the expression of pro-apoptotic proteins Bax and Cleaved-PARP, as well as phosphorylated P38 and JNK (P-P38, P-JNK), while downregulating the glycolytic enzymes HK2 and PKM2 and the anti-apoptotic protein Bcl-2 (all P < 0.05). Total JNK and P38 levels remained unchanged. The TUNEL assay further confirmed concentration-dependent enhancement of apoptosis, with a marked increase in TUNEL-positive cells at 40 μmol/L. Combined bioinformatic and experimental evidence indicates that curcumin inhibits glycolysis and promotes osteosarcoma cell apoptosis primarily through activation of the JNK/P38 MAPK signaling branch.