Ouabain signaling in oral squamous cell carcinoma cells
| Autor: | Tomohiko Ishigami, Mariko Ohtsu, Satsuki Saito, Masatake Asano |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Chemistry
NF-kappa B Interleukin 030206 dentistry Molecular biology Ouabain Transcription Factor AP-1 03 medical and health sciences 0302 clinical medicine Cell culture Carcinoma Squamous Cell medicine Humans Phosphorylation Mouth Neoplasms Secretion Signal transduction General Dentistry Transcription factor 030217 neurology & neurosurgery Signal Transduction medicine.drug Cardiac glycoside |
| Zdroj: | Journal of Oral Science. 61:498-503 |
| ISSN: | 1880-4926 1343-4934 |
| DOI: | 10.2334/josnusd.18-0411 |
| Popis: | Accurate evaluation of the anti-cancer effects of ouabain, a cardiac glycoside, requires an understanding of its signaling pathway. This study examined the effects of ouabain stimulation on spontaneous interleukin (IL)-8 and IL-1α secretion in the HSC3 oral squamous cell carcinoma cell line. IL-8 secretion was reduced and IL-1α secretion was increased in the cells. Real-time polymerase chain reaction confirmed that these changes were regulated at the transcriptional level. Further analysis revealed that ouabain stimulation induced phosphorylation of activator protein (AP)-1 components (c-Jun and c-Fos) but not nuclear factor kappa B (NF-κB) components (p65 and p50). A luciferase assay demonstrated that the NF-κB-binding site located at 1 kb upstream of the TATA box in the IL-8 gene contributed to the reduction in IL-8 secretion. Pre-incubation of the cells with BAPTA-AM and L-glutathione increased IL-8 secretion, which indicates that Ca2+ ions and reactive oxygen species are associated with the ouabain-mediated reduction in IL-8 levels. The inhibitory effect of ouabain was attributed to reduced nuclear translocation of the NF-κB p65 subunit. Taken together, these findings indicate that ouabain exerts opposing effects on transcription factors NF-κB and AP-1. |
| Databáze: | OpenAIRE |
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