title: Activation of K(+) channel by 1-EBIO rescues the head and neck squamous cell carcinoma cells from Ca(2+) ionophore-induced cell death.
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 different cell lines; SNU-1076, OSC-19 and HN5. Treatment with 1 µM 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 Ca(2+) overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Ming Zhe
authors.initials: MZ
authors.lastname: Yin
authors.affiliation: Department of Otolaryngology, Seoul National University Hospital, Seoul 03080, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Tae Wook
authors.initials: TW
authors.lastname: Kang
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: Chung-Ang University Red Cross College of Nursing, Seoul 06974, Korea.
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Yoo
authors.affiliation: Department of Otolaryngology, Seoul National University Hospital, Seoul 03080, Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Otolaryngology, Seoul National University Hospital, Seoul 03080, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: J Hun
authors.initials: JH
authors.lastname: Hah
authors.affiliation: Department of Otolaryngology, Seoul National University Hospital, Seoul 03080, Korea.; Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Myung Hun
authors.initials: MH
authors.lastname: Sung
authors.affiliation: Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea.; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea.; Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
authors.forename: Sung Joon
authors.initials: SJ
authors.lastname: Kim
keywords: 1-EBIO; Ca2+-activated K+ channel; Ionomycin; Proliferation; Squamous cell cancer