THE EFFECT OF NICLOSAMIDE ON THE HEAD AND NECK CARCINOMA CELLS SURVIVAL AND THE EXPRESSION OF WNT/β-CATENIN SIGNALING AND GLYCOLYSIS PATHWAY COMPONENTS

The aim of this study was to evaluate the effect of niclosamide, an antihelminthic drug recently identified as potential anti-cancer agent, on head and neck squamous carcinoma cells (HNSCC) viability, cell cycle distribution and apoptosis. The expression of key components of Wnt (CTNNB1, GSK-3β, CCND1, c-MYC, MMP7, BIRC5, Axin2) and glycolysis (GLUT1, MCT1, HK2, PFKM, PKM2, PDHA1, PDK1, LDHA) pathways was also examined to assess possible involvement in niclosamide anti-carcinogenic activity. HNSCC cells (FaDu, BICR6, H314 lines) were used in the research. Niclosamide treatment affected hypopharyngeal FaDu cells to the most extent (IC50 = 0.40 µM), while H314 cells derived from the floor of mouth were the least sensitive (IC50 = 0.94 µM). In FaDu cells the increased percentage of the cells in the S phase was observed along with the induction of apoptosis. Treatment with niclosamide in FaDu cells reduced the expression of MMP7 and the majority of glycolytic genes except increased LDHA. These results indicate that niclosamide is efficient inhibitor of HNSCC cells viability, however this effect depends on the cell type. In FaDu cells, the most sensitive to its anti-proliferative effect and prone to cell cycle arrest and apoptosis, this effect might be related to slightly modulation of canonical Wnt signaling and increased expression of LDHA.