Korean J Physiol Pharmacol.  2016 Jan;20(1):25-33. 10.4196/kjpp.2016.20.1.25.

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

Affiliations
  • 1Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sjoonkim@snu.ac.kr
  • 2Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 3Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 4Department of Otolaryngology, Seoul National University Hospital, Seoul 03080, Korea.
  • 5Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
  • 6Chung-Ang University Red Cross College of Nursing, Seoul 06974, Korea.

Abstract

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 Ca(2+)-activated K+ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 microM 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. Consistent 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.

Keyword

Ca(2+)-activated K+ channel; Ionomycin; Proliferation; Squamous cell cancer; 1-EBIO
Full Text Links
  • KJPP
Share
  • Twitter
  • Facebook
Copyright © 2020 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr