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

<jats:title>ABSTRACT</jats:title><jats:p>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.</jats:p>