Ouabain signaling in oral squamous cell carcinoma cells

Satsuki Saito, Mariko Ohtsu, Masatake Asano, Tomohiko Ishigami

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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-medi-ated reduction in IL-8 levels. The inhibitory effect of ouabain was attributed to reduced nuclear transloca-tion of the NF-κB p65 subunit. Taken together, these findings indicate that ouabain exerts opposing effects on transcription factors NF-κB and AP-1.

Original languageEnglish
Pages (from-to)498-503
Number of pages6
JournalJournal of Oral Science
Issue number4
Publication statusPublished - 2019


  • AP-1
  • NF-κB
  • Oral squamous cell carcinoma
  • Ouabain


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