EF-24, a Curcumin Analogue, Could Inhibit HSP90 and Induce Apoptosis-Mediated by Autophagy/Inflammation/Oxidative Stress in Papillary Thyroid Cancer Cell Lines

Abstract

Objective Papillary thyroid cancer (PTC) is one of the most common thyroid cancers and its prevalence has increased in recent years. Studies have shown that autophagy, angiogenesis, inflammation, oxidative damage, apoptosis, and some signaling pathways such as PI3K/AKT/mTOR play an important role in cancer progression. Moreover, most of their signaling molecules are the clients of heat shock protein 90 (HSP90), and its inhibition attenuates tumorigenesis. Diphenyl difluoroketone (EF-24), a curcumin analog, has antioxidative, anti-inflammatory, and anticancer properties and, unlike curcumin, has high efficacy, and may treat PTC. Therefore, the antioxidant, anti-inflammatory, angiogenic, apoptotic, and anticancer effects of EF-24 on PTC cell lines (BCPAP and TPC-1) were investigated in this study. Methods In this study, the effect of different concentrations of EF-24 and cisplatin on cell viability, apoptosis, inflammation, autophagy, oxidative status, and angiogenesis, along with HSP90 expression was evaluated in BCPAP and TPC-1 cell lines. Results The results showed that treatment with different EF-24 concentrations could significantly decrease cell viability by inducing apoptosis. EF-24 (40 µg/mL) also significantly downregulated HSP90 and the gene and protein involved in oxidative damage, angiogenesis, inflammation, and autophagy. Conclusions In conclusion, EF-24 could decrease cell viability by inducing apoptosis mediated by autophagy, oxidative stress, angiogenesis, inflammation, and the PI3K/AKT/mTOR pathway. It is possible that a decrease in HSP90 may mediate these effects. These results indicate that EF-24 is a viable option for the prevention and treatment of PTC.