Cinobufagin suppresses malignant progression of oral squamous cell carcinoma through inhibition of p65 nuclear translocation.

OBJECTIVES

Oral squamous cell carcinoma (OSCC) is characterized by aggressive biological behavior and limited therapeutic responsiveness. In this study, the objectives were to investigate the effects of cinobufagin (CBG) on the progression of OSCC, and to elucidate the underlying molecular mechanisms.

METHODS

The effects of CBG on OSCC cells were evaluated using in vitro assays to assess cell proliferation, clonogenic growth, apoptosis, migration, and invasion. Nuclear factor-kappa B (NF-κB) signaling activity was determined by immunoblotting, luciferase reporter assay, and p65 subcellular localization. The antitumor activity of CBG was further assessed in a xenograft mouse model, and its potential toxicity was evaluated by histological examination of the major organs.

RESULTS

CBG treatment suppressed proliferation and clonogenic capacity of OSCC cells, while promoting apoptotic cell death. In addition, CBG significantly reduced the migratory and invasive abilities of OSCC cells. Mechanistically, CBG attenuated NF-κB signaling by decreasing p65 phosphorylation and inhibiting its nuclear translocation, resulting in reduced NF-κB transcriptional activity. Pharmacological activation of NF-κB partially reversed the antitumor effects of CBG. Moreover, CBG markedly inhibited in vivo tumor growth, and no histological toxicity was observed.

CONCLUSIONS

CBG suppressed the malignant progression of OSCC, in vitro and in vivo. Its antitumor effects are associated with inhibition of p65 nuclear translocation and attenuation of NF-κB signaling, suggesting that CBG may represent a potential therapeutic candidate for OSCC.