Suppressive function of low-dose deguelin on the invasion of oral cancer cells by downregulating tumor necrosis factor alpha-induced nuclear factor-kappa B signaling.

Abstract

Deguelin has both antiproliferation and antimetastasis activities. However, high-dose deguelin elicits many undesired side effects. The purpose of this study was to investigate whether the low-dose deguelin can prevent the metastasis of oral cancer. The dose effects of deguelin on metastasis of oral cancer cells were analyzed by in vitro invasion assay and an orthotropic xenograft mouse model. The involvement of tumor necrosis factor alpha (TNF-α)-induced nuclear factor-kappa B (NF-κB) signaling was examined by Western blot and reporter assay. Low-dose deguelin, which has minimal cytotoxicity, significantly inhibited the invasion and migration of oral cancer cells. These inhibitory effects of low-dose deguelin were mediated by suppressing TNF-α-induced activation of IκB kinase leading to the inhibition of IκB phosphorylation, NF-κB transcriptional activity, and matrix metalloproteinase-2 (MMP2) expression. The low-dose deguelin treatment significantly inhibited tumor growth and invasion without systemic toxicity. The low-dose deguelin suppressed the invasion and migration of oral cancer by downregulating TNF-α-induced NF-κB signaling. © 2015 Wiley Periodicals, Inc. Head Neck 38: E524-E534, 2016.