Yu-Peng Liu1,2,3, Jih-Jong Lee4, Tsung-Ching Lai3, Chien-Hsin Lee3, Ya-Wen Hsiao5, Po-Shen Chen6, Wei-Ting Liu7, Chi-Yuan Hong8, Se-Kwan Lin8, Mark-Yen Ping Kuo8, Pei-Jung Lu9, Michael Hsiao3. 1. Department of Genome Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 2. Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan. 3. Genomics Research Center, Academia Sinica, Taipei, Taiwan. 4. Department of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University, Taipei, Taiwan. 5. Department of Cardiology, Taipei Veterans General Hospital, Taipei, Taiwan. 6. Graduate School of Biomedical Sciences, University of Massachusetts Medical School, Worcester, Massachusetts. 7. Institute of Pharmacology, National Cheng-Kung University, Tainan, Taiwan. 8. Institute of Clinical Dentistry, School of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. 9. Institute of Clinical Medicine, National Cheng-Kung University, Tainan, Taiwan.
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.
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.