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Activation of Ca 2+ ‐activated K + channel (SK4) Rescues Squamous Cancer Cells from Iononmycin‐induced Cell Death
Author(s) -
Yin Ming Zhe,
Park SeokWoo,
kang Tea Wook,
Kim Kyung Soo,
Lee Junho,
Hah J Hun,
Sung Myung Hun,
Kim Sung Joon
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.844.15
Subject(s) - ionomycin , hyperpolarization (physics) , chemistry , cancer research , activator (genetics) , intracellular , head and neck squamous cell carcinoma , biophysics , microbiology and biotechnology , cancer , medicine , biochemistry , biology , head and neck cancer , stereochemistry , receptor , nuclear magnetic resonance spectroscopy
The ion channels in cancer cells are drawing attention regarding cell proliferation and migration. Intracellular Ca 2+ ([Ca 2+ ]i)‐dependent signaling has crucial influence to the fate of cancer. Here we investigate the role of Ca 2+ ‐activated K+ channels in head and neck squamous carcinoma cells (HNSCC); SNU‐1076, OSC‐19 and HN5. Treatment with 1 μM ionomycin (24‐48 h) induced cell death in all the three cell lines. Whole‐ cell patch clamp study revealed the functional expression of Ca 2+ ‐activated Cl ‐ chan‐ nels (CaCC, Ano‐1) and Ca 2+ ‐activated nonselective cation channels (CAN). Ca 2+ ‐ activated K + channel (SK4) activity was variable between cell lines; at a raised[Ca 2+ ]i (0.6 μM) or with 1 μM ionomycin, only SNU‐1076 showed prominent SK4 current (I SK4 ). However, an application of SK4 activator (1‐EBIO) induced robust I SK4 with membrane hyperpolarization in OSC‐19 as well as SNU‐1076 while not in in HN5 cells. The EBIO‐induced I SK4 was completely suppressed by TRAM‐34, a selec‐tive SK4 blocker. Interestingly, the ionomycin‐induced cell death was effectively prevented by 1 ‐ 30 μM 1‐EBIO in SNU‐1076 and OSC‐19. Consistently, the rescue effect was annihilated by combined treatment with TRAM‐34. The rescue by 1‐EBIO was not effective in HN5. Above results newly demonstrate the role of SK4 and membrane hyperpolarization in HNSCCs' proliferation and death. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti‐cancer strategy in HNSCC.