1. SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca2+ signaling in nasopharyngeal carcinoma cells.
- Author
-
Jinyan Zhang, Jiazhang Wei, Qian He, Yan Lin, Rong Liang, Jiaxiang Ye, Zhe Zhang, and Yongqiang Li
- Subjects
APOPTOSIS inducing factor ,PROGRAMMED cell death 1 receptors ,CELL cycle ,CALCIUM ions ,CARCINOGENS ,CANCER invasiveness ,CANCER treatment ,MEDICAL care - 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 storeoperated Ca2+ entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC) cells. However, the effects of pharmacological blocker on other Ca2+ signaling-regulated malignant characteristics in NPC cells remained poorly understood. Methods: We examined the effects of SKF96365, an inhibitor of store-operated Ca2+ channel, on EGF-launched Ca2+ 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 Ca2+ release from endoplasmic reticulum and the subsequent Ca2+ influx. SKF96365 alone stimulated Ca2+ responses merely due to endoplasmic reticulum-released Ca2+ . SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca2+ signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway. Conclusion: SKF96365 exerts multiple antitumor activities through the distraction on the oncogenic Ca2+ signaling transduction in NPC cells. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
- View/download PDF