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SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca2+ signaling in nasopharyngeal carcinoma cells.
- Source :
-
OncoTargets & Therapy . 2015, Vol. 8, p3123-3133. 11p. - Publication Year :
- 2015
-
Abstract
- Background: Aberrant modulation of store-operated calcium ions (Ca2+) 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]
Details
- Language :
- English
- ISSN :
- 11786930
- Volume :
- 8
- Database :
- Academic Search Index
- Journal :
- OncoTargets & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 110796833
- Full Text :
- https://doi.org/10.2147/OTT.S92005