Curcumin Analog <scp>GO</scp>‐<scp>Y030</scp> Triggers <scp>JNK</scp> and p38 Signalling to Activate Apoptotic Cascades in Human Osteosarcoma Cells

Osteosarcoma, the most common primary bone cancer in adolescents, often carries a grim prognosis due to its high metastatic potential. Due to its low bioavailability, curcumin limits its adjuvant efficacy in improving prognosis and long-term survival in osteosarcoma patients. To investigate apoptosis induced by the synthesised curcumin analog GO-Y030 in human osteosarcoma cells, flow cytometry, annexin V-fluorescein isothiocyanate-labelled/propidium iodide staining, human apoptosis array, and Western blotting were used. GO-Y030 dose-dependently reduced viability and induced sub-G1 arrest and apoptosis in human osteosarcoma U2OS and 143B cells. GO-Y030 significantly activated caspases 8, 9, and 3, while suppressing cellular inhibitors of apoptosis protein 1 (cIAP-1) and X-chromosome-linked IAP. GO-Y030 increased the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2, and p38. Inhibitors of JNK (JNK-IN-8) and p38 (SB203580) suppressed GO-Y030-induced cleavage of caspases 8, 9, and 3, whereas co-treatment with the ERK inhibitor (U0126) did not lessen their activation. Overall, GO-Y030 triggers both extrinsic and intrinsic apoptotic cascades in U2OS and 143B cells by activating the JNK1/2 and p38 pathways, shedding light on its mechanism of action against human osteosarcoma cells.