Abstract
Background
Nasopharyngeal carcinoma (NPC) is a highly invasive form of head and neck cancer that arises from nasopharyngeal epithelial cells. The treatment of advanced NPC with radiotherapy presents significant challenges due to cellular resistance, which has spurred interest in natural small molecule drugs. Celastrol and curcumin, both derived from plants, have exhibited anti-tumor properties. However, the clinical development of celastrol is hindered by its low bioavailability and associated toxic side effects, while curcumin, although non-toxic, also suffers from limited bioavailability. The combination of drugs is a fundamental principle of traditional Chinese medicine, as it enhances therapeutic efficacy while reducing toxicity, suggesting a potential synergistic use of celastrol and curcumin. Furthermore, ferroptosis is crucial for tumor cell death. Consequently, our study aims to investigate whether the combination of celastrol and curcumin can induce ferroptosis in NPC cells and assess its antiproliferative effects.
Methods
Human nasopharyngeal carcinoma cell lines were used for in vitro cell analysis. CCK8 was used to evaluate the effect of treatment with different concentrations of Celastrol and curmin on cell viability in a human nasopharyngeal carcinoma CNE1 cell line. Mitochondrial reactive oxygen species and mitochondrial membrane potential were detected to determine mitochondrial oxidative stress and function. Western blot was used to detect apoptosis, autophagy and ferritin-related proteins expression.
Results
The combination of celastrol and curcumin exhibited a more pronounced antiproliferative effect on CNE1 cells. Following treatment with these compounds, mitochondria generated substantial amounts of reactive oxygen species, resulting in impaired mitochondrial function. Moreover, the cell death induced by the combination of celastrol and curcumin was found to be independent of apoptosis, instead, it was correlated with increased cellular autophagy, enhanced mitochondrial fission, and the induction of ferroptosis.
Conclusion
Low doses of celastrol combined with curcumin exhibited a greater inhibition of CNE1 cell growth compared to curcumin alone. This enhanced efficacy of the combination therapy is likely attributable to its effects on mitochondrial fission and the induction of ferroptosis.