title: SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca(2+) signaling in nasopharyngeal carcinoma cells.
abstract: BACKGROUND
  Aberrant modulation of store-operated calcium ions (Ca(2+)) entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca(2+) entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC) cells. However, the effects of pharmacological blocker on other Ca(2+) signaling-regulated malignant characteristics in NPC cells remained poorly understood.
  
  
  METHODS
  We examined the effects of SKF96365, an inhibitor of store-operated Ca(2+) channel, on EGF-launched Ca(2+) signaling in two NPC cell lines. We determined the effects of SKF96365 on cell proliferation, colony formation, apoptosis, and cell-cycle status in vitro. We further elucidated the antitumor activity of SKF96365 in xenograft-bearing mice.
  
  
  RESULTS
  It was found that SKF96365 disturbed the thapsigargin (TG)-stimulated Ca(2+) release from endoplasmic reticulum and the subsequent Ca(2+) influx. SKF96365 alone stimulated Ca(2+) responses merely due to endoplasmic reticulum-released Ca(2+). SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca(2+) signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway.
  
  
  CONCLUSIONS
  SKF96365 exerts multiple antitumor activities through the distraction on the oncogenic Ca(2+) signaling transduction in NPC cells.
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Jinyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Otolaryngology-Head and Neck Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
authors.forename: Jiazhang
authors.initials: J
authors.lastname: Wei
authors.affiliation: Graduate School of Information Science and Technology, Hokkaido University, Sapporo, Japan.
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Jiaxiang
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Affiliated Cancer Hospital of Guangxi Medical University, Nanning, People's Republic of China.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Li
keywords: EGF signaling; caspase-7; caspase-9; store-operated Ca2+ entry