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
Journal
Head and Neck
Journal Volume
38
Pages
E524-E534
Date Issued
2016
Author(s)
Liu Y.-P.
Lee J.-J.
Lai T.-C.
Lee C.-H.
Hsiao Y.-W.
Chen P.-S.
Liu W.-T.
Hong C.-Y.
Lu P.-J.
Hsiao M.
Abstract
Background 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. Methods 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. Results 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. Conclusion The low-dose deguelin suppressed the invasion and migration of oral cancer by downregulating TNF-α-induced NF-κB signaling. ? 2015 Wiley Periodicals, Inc..
SDGs
Other Subjects
antimetastatic agent; cell nucleus DNA; deguelin; dimethyl sulfoxide; gelatinase A; I kappa B beta; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein kinase B; tumor necrosis factor alpha; deguelin; gelatinase A; immunoglobulin enhancer binding protein; rotenone; tumor necrosis factor; animal experiment; animal model; Article; bioluminescence; cancer inhibition; cancer staging; cell cycle; cell differentiation; cell growth; cell migration; cell motility; cell proliferation; cell viability; controlled study; cytotoxicity; dose response; down regulation; drug dose comparison; drug megadose; early cancer; enzyme activation; female; IC50; in vitro study; in vivo study; low drug dose; metastasis; mouse; mouth cancer; multiple cycle treatment; nonhuman; oral cancer cell line; priority journal; protein degradation; protein expression; protein phosphorylation; signal transduction; transcription initiation; tumor growth; tumor invasion; tumor volume; tumor xenograft; Western blotting; analogs and derivatives; animal; antagonists and inhibitors; drug effects; drug screening; human; metabolism; mouth tumor; nonobese diabetic mouse; pathology; SCID mouse; tumor cell line; tumor invasion; Animals; Cell Line, Tumor; Female; Humans; Matrix Metalloproteinase 2; Mice; Mice, Inbred NOD; Mice, SCID; Mouth Neoplasms; Neoplasm Invasiveness; NF-kappa B; Rotenone; Signal Transduction; Tumor Necrosis Factor-alpha; Xenograft Model Antitumor Assays
Publisher
John Wiley and Sons Inc.
Type
journal article