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Low Dose Deguelin Suppresses In‐situ Oral Cancer Meatstasis through Down Regulation of Akt‐independent NF‐kB Signaling
Author(s) -
Jan YiHua,
Lai TsungChing,
Chiu Tony,
Chang JengShou,
Hsiao Michael
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.964.8
Subject(s) - protein kinase b , chemistry , cell growth , apoptosis , cancer research , viability assay , pharmacology , biology , biochemistry
Deguelin, a rotenoid from Mundulea sericea, has a diversity of antitumor activities. Previous studies have shown deguelin inhibited tumor cell proliferation by inducing apoptosis through the inhibition of Akt signaling. However, the anti‐metastatic effects of deguelin have not been explored. In this study, we evaluated low dose deguelin (IC 10 ) effects on oral cancer cells invasion/migration potentials in vitro and on in‐situ oral cancer animal model. Our results showed deguelin significantly inhibited the invasion and migration ability of oral cancer cells at low dose with no cytotoxic effects as evaluated by cell viability, proliferation and cell cycle distribution analyses. Western blot analysis showed low dose deguelin did not alter the phosphorylation level of AKT in SAS and CA922 cell lines. However, low dose deguelin suppressed the activation of IκB kinase and led to the sequential inhibition of IκB phosphorylation. Low dose deguelin also suppressed the NF‐κB reporter activity in a dose‐dependent and time‐dependent manner. Furthermore, in vivo study showed that low dose deguelin treatment significantly inhibited the orthotopic xenograft tumor growth and tumor invasion with no systemic toxicity and body weight loss. In conclusions, our data showed low dose deguelin inhibited the invasion/migration of oral cancer in vitro and in‐situ by Akt‐independent downregulation of NF‐κB signaling. These findings may have clinical implications in utilizing deguelin to treat metastatic oral cancers.