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

Combined treatment significantly reduced cell viability and induced apoptotic morphological changes, which were confirmed by increased sub-G1 population, enhanced DNA fragmentation, and elevated cleaved poly(ADP-ribose) polymerase (PARP) levels. Mechanistically, combined treatment markedly increased c-Jun N-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.