Activation of K+ channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca2+ ionophore-induced cell death.
10.4196/kjpp.2016.20.1.25
- Author:
Ming Zhe YIN
1
;
Seok Woo PARK
;
Tae Wook KANG
;
Kyung Soo KIM
;
Hae Young YOO
;
Junho LEE
;
J Hun HAH
;
Myung Hun SUNG
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. sjoonkim@snu.ac.kr
- Publication Type:Original Article
- Keywords:
Ca(2+)-activated K+ channel;
Ionomycin;
Proliferation;
Squamous cell cancer;
1-EBIO
- MeSH:
Carcinoma, Squamous Cell*;
Cell Death*;
Cell Line;
Cell Proliferation;
Head*;
Ion Channels;
Ionomycin;
Neck*;
Neoplasms, Squamous Cell
- From:The Korean Journal of Physiology and Pharmacology
2016;20(1):25-33
- CountryRepublic of Korea
- Language:English
-
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.