Activation of K⁺ channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca²⁺ ionophore-induced cell death

Activation of K⁺ channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca²⁺ ionophore-induced cell death

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca²⁺ ([Ca²⁺]_i)-dependent signaling affects the fate of cancer cells. Here we investigate the role of Ca²⁺-activated K⁺ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of dif-ferent cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 μM ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of Ca²⁺-activated Cl^− channels (Ano-1) and Ca²⁺-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward K⁺ current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Con-sistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the Ca²⁺ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.