Combined Curcumin and Doxorubicin Induce Apoptosis via JNK-Dependent MAPK Signaling Independent of TXNDC5 in Human Osteosarcoma Cells

BACKGROUND: Curcumin, a dietary polyphenol with anticancer potential, has been reported to enhance the efficacy of chemotherapeutic agents. METHODS: The effects of combined curcumin and doxorubicin treatment on apoptosis and associated signaling pathways were investigated in human osteosarcoma HOS cells. RESULTS: -terminal kinase (JNK) phosphorylation, whereas extracellular signal-regulated kinase (ERK) phosphorylation showed no appreciable change. Pharmacological inhibition revealed that JNK suppression attenuated PARP cleavage, while ERK inhibition also reduced apoptotic responses, suggesting a permissive role of basal ERK activity. In addition, combined treatment was associated with increased expression of the endoplasmic reticulum stress marker GRP78 and modulation of autophagy-associated markers. Although thioredoxin domain-containing protein 5 (TXNDC5) expression was reduced, TXNDC5 overexpression failed to attenuate apoptosis, indicating that apoptosis induction occurs independently of TXNDC5. CONCLUSIONS: These findings indicate that combined curcumin and doxorubicin induce apoptosis primarily through JNK-dependent MAPK signaling, accompanied by stress-associated cellular responses.