The Combination of Celastrol and Curcumin Enhances the Antitumor Effect in Nasopharyngeal Carcinoma by Inducing Ferroptosis

Nasopharyngeal carcinoma (NPC) is a highly invasive form of head and neck cancer that arises from nasopharyngeal epithelial cells. Celastrol and curcumin, both derived from traditional Chinese medicine, have demonstrated antitumor potential. However, the clinical application of these compounds is limited by their low bioavailability and/or toxicity. Cancer cell viability, apoptosis, autophagy, ferroptosis, and mitochondrial fission- and fusion-related proteins were evaluated following treatment with celastrol alone, curcumin alone, and their combination. The results indicated that low doses of celastrol (0.7 μM) alone do not inhibit proliferation in NPC cells. However, when combined with curcumin, there is a significant enhancement of the antiproliferative effect. There was no significant alteration in the expression levels of the apoptosis-related proteins BCL2-associated X and cleaved caspase 3 in either the curcumin alone or the combined treatment groups compared to the control group. Interestingly, the combined treatment significantly increased the ferroptosis contributor acyl-CoA synthetase long-chain family member 4 while notably decreasing solute carrier family 7 member 11 and glutathione peroxidase 4, accompanied by increased phosphorylation of dynamin-related protein 1. Furthermore, the combined treatment exhibited significant antitumor efficacy with low toxic side effects in a xenograft model. In conclusion, our study provides new insights into combination therapies to enhance anti-NPC efficacy.