Nobiletin and 5‑demethylnobiletin ameliorate hypopharyngeal squamous cell carcinoma by suppressing TGF‑β‑mediated epithelial‑mesenchymal transition

Hypopharynx squamous cell carcinoma accounts for 5% of all diseases diagnosed in Mexico. It is associated with poor oral hygiene, alcohol consumption and tobacco use and is usually diagnosed at an advanced stage, with metastasis to the lymph nodes. Metastasis from primary tumors occurs via a complex process called epithelial-mesenchymal transition (EMT), in which epithelial cells gradually acquire characteristics of mesenchymal cells, enabling their spread. Flavonoids have anticancer effects. In the present study, the effects of the polymethoxyflavones nobiletin (Nob) and 5-demethylnobiletin (5-DMN) on transforming growth factor (TGF)-β1-induced EMT in hypopharyngeal squamous cell carcinoma cells were evaluated. Either polymethoxyflavone alone inhibited cell proliferation and combined treatment had no synergistic effect. The two flavonoids inhibited EMT by reversing the effects of TGF-β on morphological changes, migration and the expression of the markers E-cadherin, N-cadherin, Slug and Snail. Thus, Nob and 5-DMN are potential candidates for use in the treatment of oral squamous cell carcinoma.