Rescue effects of small conductance Ca2+-activated K+ channel (SK4) activator on the Ca2+ overload induced death of head and neck cancer cells

Abstract

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular Ca2+ ([Ca2+]c)-dependent signaling affects the fate of cancer cells. K+ channels play critical roles in proliferation and apoptosis in many types of cancer cells. Small conductance Ca2+ activated K+ channel (SK4) is founded to be functional expressed in head and neck cancer cell carcinoma cells. The role of Ca2+-activated K+ channel (SK4) in head and neck squamous cell carcinoma (HNSCC) were investigated different cell lines

SNU-1076, OSC-19 and HN5 . Treatment with 1 μΜ ionomycin (Ca2+ ionophore) induced cell death in all of 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. Consistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results demonstrate the role of SK4 in the fate of HNSCC under the Ca2+ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.