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

  • Yin, Ming Zhe (Department of Physiology, Seoul National University College of Medicine) ;
  • Park, Seok-Woo (Department of Otolaryngology, Seoul National University Hospital) ;
  • Kang, Tae Wook (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Kyung Soo (Department of Physiology, Seoul National University College of Medicine) ;
  • Yoo, Hae Young (Chung-Ang University Red Cross College of Nursing) ;
  • Lee, Junho (Department of Otolaryngology, Seoul National University Hospital) ;
  • Hah, J. Hun (Department of Otolaryngology, Seoul National University Hospital) ;
  • Sung, Myung Hun (Department of Otolaryngology, Seoul National University Hospital) ;
  • Kim, Sung Joon (Department of Physiology, Seoul National University College of Medicine)
  • Received : 2015.06.05
  • Accepted : 2015.08.14
  • Published : 2016.01.01

Abstract

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$)-dependent signaling affects the fate of cancer cells. Here we investigate the role of $Ca^{2+}$-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 $1{\mu}M$ ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of $Ca^{2+}$-activated $Cl^-$ channels (Ano-1) and $Ca^{2+}$-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 $Ca^{2+}$ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.

Keywords

References

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