Nobiletin inhibits hypoxia-induced epithelial-mesenchymal transition in renal cell carcinoma cells

J Cell Biochem. 2019 Feb;120(2):2039-2046. doi: 10.1002/jcb.27511. Epub 2018 Sep 11.


Hypoxia is a universal characteristic of solid tumor and involving cancer metastasis via epithelial-mesenchymal transition (EMT). Nobiletin (3',4',5,6,7,8-hexamethoxyflavone), a dietary polymethoxylated flavonoid found in citrus fruits, has been reported to have anticancer effects. However, the possible role of nobiletin in renal cell carcinoma (RCC) remains unclear. Thus, the aim of this study was to identify the effect of nobiletin on hypoxia-induced EMT in RCC cells. We found that nobiletin significantly inhibited the migration and invasion induced by hypoxia in RCC cells. In addition, nobiletin reversed the hypoxia-induced EMT process in RCC cells. Furthermore, nobiletin suppressed the activation of NF-κB and Wnt/β-catenin signaling pathways in hypoxia-stimulated RCC cells. In conclusion, these findings demonstrate that nobiletin inhibits hypoxia-induced EMT in human RCC cells via the inactivation of the NF-κB and Wnt/β-catenin signaling pathways.

Keywords: epithelial-mesenchymal transition (EMT); hypoxia; nobiletin; renal cell carcinoma (RCC).